Hypertensive disorders of pregnancy and risk of Alzheimer’s disease, vascular dementia, and other related dementia

Several recent studies have examined whether hypertensive disorders of pregnancy (HDP) are associated with an increased risk for Alzheimer’s disease (AD) and other related dementias (RD) with conflicting findings. Limitations to prior studies include lack of assessing risk by dementia subtype, inadequate sample sizes, and not fully exploring the role of mid-life factors. We performed a retrospective matched cohort study among women with >1 singleton pregnancy (1939–2013) using the Utah Population Database. HDP-exposed women (n=19,989) were one-to-two matched with unexposed women (n=39,679) by 5-year age groups, year of childbirth (within 1 year), and parity (1, 2, 3, 4, ≥5) at the time of the pregnancy. HDP pregnancies were complicated by preeclampsia (62%), gestational hypertension (34%), and eclampsia (4%). Women with a history of HDP had a higher hazard of all-cause dementia (HR=1.37; 95% CI: 1.26, 1.50) compared to women without a history of HDP after adjustment for maternal age, year of childbirth, and parity. The hazard doubled after additionally accounting for pre-pregnancy BMI (HR=2.31; 95% CI: 1.24, 4.32). Stratifying by dementia subtype, we found HDP to be associated with a higher hazard of vascular dementia (HR=1.64; 95% CI: 1.19, 2.26) and other related dementia (HR=1.49; 95% CI: 1.34, 1.65) but not Alzheimer’s disease (HR=1.04; 95% CI: 0.87, 1.24) after accounting for competing risks. Mid-life hypertension and stroke were found to have the greatest mid-life impact, mediating 43% and 41% of dementia risk, respectively, highlighting women who may most benefit from close surveillance and early preventive and clinical interventions.

Dementia subtype prediction models constructed by penalized regression methods for multiclass classification using serum microRNA expression data

There are many subtypes of dementia, and identification of diagnostic biomarkers that are minimally-invasive, low-cost, and efficient is desired. Circulating microRNAs (miRNAs) have recently gained attention as easily accessible and non-invasive biomarkers. We conducted a comprehensive miRNA expression analysis of serum samples from 1348 Japanese dementia patients, composed of four subtypes—Alzheimer’s disease (AD), vascular dementia, dementia with Lewy bodies (DLB), and normal pressure hydrocephalus—and 246 control subjects. We used this data to construct dementia subtype prediction models based on penalized regression models with the multiclass classification. We constructed a final prediction model using 46 miRNAs, which classified dementia patients from an independent validation set into four subtypes of dementia. Network analysis of miRNA target genes revealed important hub genes, SRC and CHD3, associated with the AD pathogenesis. Moreover, MCU and CASP3, which are known to be associated with DLB pathogenesis, were identified from our DLB-specific target genes. Our study demonstrates the potential of blood-based biomarkers for use in dementia-subtype prediction models. We believe that further investigation using larger sample sizes will contribute to the accurate classification of subtypes of dementia.

Creating A Research Ready Data Asset and Empowering Dynamic and Efficient Research: The Sail Dementia E-Cohort (SDEC)

IntroductionResearch can often be slow to start and require duplication of effort which in lots of cases has previously been completed to generate research-ready-data-assets (RRDA). Within the UK, two programmes: Dementias Platform UK (DPUK) that brings together over 50 different dementia-related cohorts and Secure Anonymised Information Linkage (SAIL) Databank, which provides access to longitudinal population-scale person-level data for every person in Wales have tried to tackle this challenge of creation, use and management of RRDA’s. Objectives and ApproachCombining clinical, data and management expertise from DPUK and SAIL, we hoped to construct a RRDA that was easily accessible and well described for a dementia e-cohort. Welsh residents with available primary care records were included, with clinical and demographic information including follow-up times, several dementia indicators using validated diagnostic code lists, information on every dementia-related diagnostic event and several covariates and co-morbidities. SDeC was made available to researchers and can be modified according to appropriate study designs, with learning from projects used to update the SDeC to improve future uses. Interactive visualisations effectively summarise cohort characteristics, aiding researchers to quickly determine cohort eligibility for dementia studies. ResultsSDeC contains data from 4.6 million participants in SAIL, with 1.5 million meeting cohort inclusion criteria, resulting in 24.3 million person-years of follow-up. Of these, 146,323 (10%) developed all-cause dementia during follow-up, with 90,150 (60%) having dementia subtype codes. We made this resource available to researchers who had never used SAIL before, with limited experience of population-scale routine-data, and projects have proceeded with one managing to proceed from point of initial access to submission of publication in less than 6-months. Conclusion / ImplicationsSDeC provides a reproducible dynamic method for completing dementia research, and expediting learning and understanding of the use of these data, with further developments and maintenance planned to increase the complexity and detail available to researchers over time.

Antiherpetic medication and incident dementia: observational cohort studies in four countries

IntroductionRecent meta-analysis of the association between herpesvirus infection and dementia concluded that the evidence for an association to date is insufficient.Methods2.5 million individuals aged ≥65 years were followed up using linked electronic health records in four national observational cohort studies. Exposure and outcome were classified using coded data from primary and secondary care. Data were analyzed using survival analysis with time-dependent covariates.ResultsResults were heterogeneous, with a tendency towards decreased dementia risk in individuals exposed to antiherpetic medication. Associations were not affected by treatment number, herpes subtype, dementia subtype, or specific medication. In one cohort, individuals diagnosed with herpes but not exposed to antiherpetic medication were at higher dementia risk.DiscussionShort-term antiherpetic medication is not markedly associated with incident dementia. Because neither dementia subtype nor herpes subtype modified the association, the small but significant decrease in dementia incidence with antiherpetic adminstration may reflect confounding and misclassification.

OP0201 INCREASED RISK OF DEMENTIA IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect any organ of the body. Nervous system involvement of SLE lead to a variety of neurologic and psychiatric manifestations, which are called neuropsychiatric lupus. Cognitive dysfunction may appear as part of neuropsychiatric lupus. There are several papers on the increase in dementia risk in SLE patients, but data are not sufficient and there is little data on whether SLE affects dementia differently depending on the dementia subtype.Objectives:We evaluate dementia incidence and risk in SLE patients in a nationwide population-based cohort and determine whether the risk is different for each dementia subtype.Methods:We identified patients aged 40 years or more, with systemic lupus erythematosus between 2008 and 2014 using the database of the National Health Insurance Service (NHIS) of south Korea. Patients who had previously been diagnosed with dementia were excluded from the study. A total of 11,288 SLE patients and 56,440 control subjects with a 1:5 age- and sex-matching were included in the study. The primary outcome of the study was incident dementia, which was defined by an ICD-10 code and the use of dementia medications. Kaplan-Meier curves and Cox proportional hazards regression analysis were used for the analysis.Results:The incidence rate of dementia was higher in SLE cohort (3.90 per 1,000 person-years) than control cohort (2.73 per 1,000 person-years). Incidence rates of Alzheimer disease and vascular dementia were also higher in SLE cohort than control. SLE patients had a higher risk of dementia compared to control cohorts without SLE (crude hazard ratio 1.43, 95% CI 1.25-1.63). In patients with SLE, the risk of Alzheimer’s disease was 1.4 times higher and the risk of vascular dementia 1.6 times higher than non-SLE control.Conclusion:In this nationwide population-based cohort study, SLE patients had a 1.4-fold higher risk of incident dementia compared to patients without SLE. Further studies are warranted to identify mechanisms of increased risk of dementia in SLE patients. Monitoring of dementia incidence in SLE patients is needed in clinical practice.Disclosure of Interests:None declared

The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC)

Introduction Dementia Platform UK (DPUK) brings together over 50 different dementia-related cohorts. Most studies have restricted follow-up times and all are based on information from people who volunteer time and data for research. Participants are therefore often not representative of the 'wider population' and generalization of results is complicated. The Secure Anonymised Information Linkage databank (SAIL) holds long-time information on every person in Wales registered with the national health service, so generalization of study results is easier; however, data management and analysis of SAIL data is not trivial. We used data from SAIL to construct an easily accessible, well described dementia e-cohort. Methods With some age restrictions, all Welsh residents for whom primary care data were available were included. Within SAIL, a table was created holding demographic information for every participant including follow-up times and several dementia indicators. Using validated diagnostic code lists, this table was linked to information on every dementia-related diagnostic event and several covariates and co-morbidites. SAIL-DeC can be modified according to varying study designs using annotated SQL-based scripts. Information on SAIL-DeC can easily be updated and linked to additional data on the SAIL database. Interactive visualisations effectively summarise cohort characteristics, aiding researchers to quickly determine cohort eligibility for dementia studies. Results From 4.4 million participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia during follow-up, with 77,978 (60%) having dementia subtype codes. Seventy-nine percent of participants who developed dementia died during follow-up. Median survival was 12.3 years for participants diagnosed with dementia when aged 50-60, 6.8 years when aged 60-70, 4.2 years when aged 70-80 and 2.4 years when aged 80-90. Conclusions We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.

Survival and life-expectancy in a young-onset dementia cohort with six years of follow-up: the NeedYD-study

ABSTRACTObjectives:The aim of this study was to investigate survival time and life-expectancy in people with young-onset dementia (YOD) and to examine the relationship with age, sex, dementia subtype and comorbidity.Design, Setting and Participants:Survival was examined in 198 participants in the Needs in Young-onset Dementia study, including participants with Alzheimer’s dementia (AD), vascular dementia (VaD) and frontotemporal dementia (FTD).Measures:The primary outcomes were survival time after symptom onset and after date of diagnosis. Cox proportional hazards models were used to explore the relationship between survival and age, sex, dementia subtype and comorbidity. Additionally, the impact on remaining life expectancy was explored.Results:During the six-year follow-up, 77 of the participants died (38.9%), 78 participants survived (39.4%) and 43 were lost to follow-up (21.7%). The mean survival time after symptom onset and diagnosis was 209 months (95% CI 185-233) and 120 months (95% CI 110-130) respectively. Participants with AD had a statistically significant shorter survival compared with VaD participants, both regarding survival after symptom onset (p = 0.047) as well as regarding survival after diagnosis (p = 0.049). Younger age at symptom onset or at diagnosis was associated with longer survival times. The remaining life expectancy, after diagnosis, was reduced with 51% for males and 59% for females compared to the life expectancy of the general population in the same age groups.Conclusion/Implications:It is important to consider the dementia subtype when persons with YOD and their families are informed about the prognosis of survival. Our study suggests longer survival times compared to other studies on YOD, and survival is prolonged compared to studies on LOD. Younger age at symptom onset or at diagnosis was positively related to survival but diagnosis at younger ages, nevertheless, still diminishes life expectancy dramatically.