scholarly journals Association of lipid-regulating drugs with dementia and related conditions: an observational study of data from the Clinical Practice Research Datalink

2021 ◽  
Author(s):  
Luke A McGuinness ◽  
Julian PT Higgins ◽  
Venexia M Walker ◽  
Neil M Davies ◽  
Richard M Martin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Disease Risk ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Confounding By Indication ◽  
Drug Classes ◽  
Increased Risk ◽  
Residual Confounding

Background: There is some evidence that circulating blood lipids play a role in the development of Alzheimer's disease (AD) and dementia. These modifiable risk factors could be targeted by existing lipid-regulating agents, including statins, for dementia prevention. Here, we test the association between lipid-regulating agents and incidence of dementia and related conditions in the Clinical Practice Research Datalink (CPRD), an United Kingdom-based electronic health record database. Methods: A retrospective cohort study was performed using routinely collected CPRD data (January 1995 and March 2016). Multivariable Cox proportional hazard models, allowing for a time-varying treatment indicator, were used to estimate the association between seven lipid-regulating drug classes (vs. no drug) and five dementia outcomes (all-cause, vascular and other dementias, and probable and possible Alzheimer's disease). Results: We analyzed 1,684,564 participants with a total follow-up of 10,835,685 patient-years (median: 5.9 years (IQR:2.7-9.7)). We found little evidence that lipid-regulating agents were associated with incidence of Alzheimer's disease (probable HR:0.98, 95%CI:0.94-1.01; possible HR:0.97, 95%CI:0.93-1.01), but there was evidence of an increased risk of all-cause (HR:1.17, 95%CI:1.14-1.19), vascular (HR:1.81, 95%CI:1.73-1.89) and other dementias (HR:1.19, 95%CI:1.15-1.24). Evidence from a number of control outcomes indicated the presence of substantial residual confounding by indication (ischaemic heart disease HR: 1.62, 95%CI: 1.59-1.64; backpain HR: 1.04, 95%CI: 1.03-1.05; and Type 2 diabetes HR: 1.50, 95%CI: 1.48-1.51). Conclusion: Lipid-regulating agents were not associated with reduced Alzheimer's disease risk. There was some evidence of an increased the risk of all-cause, vascular and other dementias, likely due to residual confounding by indication.

scholarly journals Infectious Disease Burden and the Risk of Alzheimer’s Disease: A Population-Based Study

2021 ◽  
pp. 1-10
Author(s):  
Antonios Douros ◽  
Christina Santella ◽  
Sophie Dell’Aniello ◽  
Laurent Azoulay ◽  
Christel Renoux ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Burden ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Cumulative Number ◽  
Increased Risk

Background: Previous studies suggested a link between various infectious pathogens and the development of Alzheimer’s disease (AD), posing the question whether infectious disease could present a novel modifiable risk factor. Objective: To assess whether infectious disease burden due to clinically apparent infections is associated with an increased risk of AD. Methods: We conducted a population-based nested case-control study using the United Kingdom Clinical Practice Research Datalink. We included all dementia-free subjects ≥50 years of age enrolling in the database between January 1988 and December 2017. Each case of AD identified during follow-up was matched with up to 40 controls. Conditional logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with ≥1 infection diagnosed >  2 years before the index date compared with no infection during the study period. We further stratified by time since first infection and cumulative number of infections. Results: The cohort included overall 4,262,092 individuals (mean age at cohort entry 60.4 years; 52% female). During a median follow-up of 10.5 years, 40,455 cases of AD were matched to 1,610,502 controls. Compared with having no burden of infectious disease, having a burden of infectious disease was associated with an increase in the risk of AD (OR, 1.05; 95% CI, 1.02 to 1.08). The risk increased with longer time since first infection, peaking after 12–30 years (OR, 1.11; 95% CI, 1.05–1.17). The risk did not increase with cumulative number of infections. Conclusion: The overall risk of AD associated with infectious disease burden was small but increased gradually with longer time since first infection.

scholarly journals AB0576 BONE EROSION IN PSORIATIC ARTHRITIS ASSOCIATED WITH PSORIASIS DURATION, SKIN, NAIL AND JOINT DISEASE SEVERITY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1325.2-1326
Author(s):  
M. Chamurlieva ◽  
E. Loginova ◽  
T. Korotaeva ◽  
Y. Korsakova ◽  
E. Gubar ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Psoriatic Arthritis ◽  
Disease Severity ◽  
Bone Erosion ◽  
Joint Disease ◽  
Practice Research ◽  
Forest Plot ◽  
Clinical Practice Research Datalink ◽  
Increased Risk ◽  
Nail Disease

Background:Psoriatic arthritis (PsA) is heterogeneous in its clinical presentation and disease course, but many patients (pts) develop a destructive form of arthritis. Psoriasis (PsO) precedes arthritis by an average of 7 years. [1]. Theory of transition from PsO to PsA has been proposed recently [2]. But association between skin disease severity and joint disease are still unclear.Objectives:to evaluate association between bone erosion, PsO duration, skin and nail disease severity in PsA pts based on data from clinical practice (RU-PsART cohort).Methods:737 (M/F=350/387) PsA pts fulfilling the CASPAR criteria were included. Mean age 47.4±12.7 years (yrs), PsA duration 55[17;120] mos., PsO duration 165[74.5;292] mos., mean DAPSA 23.3[14;36.9] mos., HAQ-DI - 0.98 [0.5;1.38], CRP - 7.4 [2.1;18] mg/l. All pts underwent standard clinical examination (tender joins count (TJC)/68, swelling joints count (SJC)/66, CRP (mg/l), DAPSA, dactylitis, enthesitis by LEI + Plantar Facia (PF), HAQ-DI. Mild disease was defined as body surface area (BSA)≤10%, moderate to severe as BSA>10%. The presence/absent of nail PsO was evaluated. X-ray of feet and hand were done in 622 out of 737 pts. The one-factor model of logistic regression was used to identify a group of features that are associated with achievement MDA. M±SD, Me [Q25; Q75], Min-Max, %, t-test, Pierson-χ2, Manna-Whitney tests, ORs with 95% CI were performed. All p<0.05 were considered to indicate statistical significance.Results:PsO precedes of PsA by an average of 9.2 years. BSA≤10% was found in 615 out of 672 pts (91.5%), BSA>10% - in 57 out of 672 pts (8.5%). Nail PsO were seen in 230 out of 737 (31.2%). Bone erosion was found in 237 out of 622 of pts (38.1%). Among these pts nail PsO were seen in 67 out of 237 pts (28.3%). Enthesitis found in 236 out of 737 pts (42.1%), dactylitis – in 197 out 731 pts (27%), axial PsA – in 315 out of 731 pts (43.1%). Bone erosion significantly associated with PsO duration more than 5 yrs., skin and nail PsO severity, high PsA activity by DAPSA, axial manifestation and duration of PsA > 36 mos. (Figure 1).Figure 1Forest plot of factors associated with bone erosion in PsA pts.Conclusion:In our cohort the majority of PsA pts had mild PsO preceded PsA on average of 9.2 yrs. Bone erosion was found in 30% of PsA pts which associated with PsO duration, skin and nail disease severity as well as with PsA activity. Early diagnosis and therapeutic intervention within a “window of opportunity” are very important for improving outcomes and prevent structural damage in PsA.References:[1]Tillett W, et al. Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort. Rheumatol. 2017; 56, 2109–2113[2]Scher JU, et al. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol. 2019;15(3):153-166. doi: 10.1038/s41584-019-0175-0. PMID: 30742092.Disclosure of Interests:None declared.

scholarly journals Alzheimer's Disease Risk Gene, GAB2, is Associated with Regional Brain Volume Differences in 755 Young Healthy Twins

2012 ◽  
Vol 15 (3) ◽  
pp. 286-295 ◽  
Author(s):  
Derrek P. Hibar ◽  
Neda Jahanshad ◽  
Jason L. Stein ◽  
Omid Kohannim ◽  
Arthur W. Toga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Young Adult ◽  
Disease Risk ◽  
Adult Brain ◽  
Brain Morphology ◽  
Control Analysis ◽  
Risk Gene ◽  
Increased Risk ◽  
The Brain

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27–1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.

CYP46A1 variants influence Alzheimer’s disease risk and brain cholesterol metabolism

2009 ◽  
Vol 24 (3) ◽  
pp. 183-190 ◽  
Author(s):  
Heike Kölsch ◽  
Dieter Lütjohann ◽  
Frank Jessen ◽  
Julius Popp ◽  
Frank Hentschel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Cholesterol Metabolism ◽  
Disease Risk ◽  
Brain Cholesterol ◽  
Increased Risk ◽  
Csf Levels ◽  
Interaction Term ◽  
Gene Variability

AbstractBackgroundCholesterol 24S-hydroxylase (CYP46) catalyzes the conversion of cholesterol to 24S-hydroxycholesterol, the primary cerebral cholesterol elimination product. Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer’s disease (AD) and results are contradictory.MethodsWe performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.ResultsTwo of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p = 0.016; rs4900442: p = 0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p = 0.006). Haplotypes including both SNPs were calculated and haplotype G–C was identified to influence the risk of AD (p = 0.005). AD patients and non-demented controls, who were carriers of the G–C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p = 0.001) and cholesterol (p < 0.001).ConclusionOur results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.

scholarly journals Androgen Deprivation Therapy and Future Alzheimer’s Disease Risk

2016 ◽  
Vol 34 (6) ◽  
pp. 566-571 ◽  
Author(s):  
Kevin T. Nead ◽  
Greg Gaskin ◽  
Cariad Chester ◽  
Samuel Swisher-McClure ◽  
Joel T. Dudley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Propensity Score ◽  
Medical Record ◽  
Disease Risk ◽  
Medical Record Data ◽  
Electronic Medical Record Data ◽  
Increased Risk ◽  
Record Data

Purpose To test the association of androgen deprivation therapy (ADT) in the treatment of prostate cancer with subsequent Alzheimer’s disease risk. Methods We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mt. Sinai hospitals. Specifically, we extracted International Classification of Diseases-9th revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. We then tested the effect of ADT on risk of Alzheimer’s disease using 1:5 propensity score–matched and traditional multivariable-adjusted Cox proportional hazards models. The duration of ADT use was also tested for association with Alzheimer’s disease risk. Results There were 16,888 individuals with prostate cancer meeting all inclusion and exclusion criteria, with 2,397 (14.2%) receiving ADT during a median follow-up period of 2.7 years (interquartile range, 1.0-5.4 years). Propensity score–matched analysis (hazard ratio, 1.88; 95% CI, 1.10 to 3.20; P = .021) and traditional multivariable-adjusted Cox regression analysis (hazard ratio, 1.66; 95% CI, 1.05 to 2.64; P = .031) both supported a statistically significant association between ADT use and Alzheimer’s disease risk. We also observed a statistically significant increased risk of Alzheimer’s disease with increasing duration of ADT (P = .016). Conclusion Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer’s disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.

Comparative effect of statins on the risk of incident Alzheimer disease

Neurology ◽  
2017 ◽  
Vol 90 (3) ◽  
pp. e179-e187 ◽  
Author(s):  
Liliya Sinyavskaya ◽  
Serge Gauthier ◽  
Christel Renoux ◽  
Sophie Dell'Aniello ◽  
Samy Suissa ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Alzheimer Disease ◽  
Proportional Hazards ◽  
Neuroprotective Effect ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Sensitivity Analyses ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Increased Risk

ObjectiveTo investigate whether fungus-derived statins are associated with a lower risk of incident Alzheimer disease (AD) compared with synthetic statins using real-world clinical practice data.MethodsWe identified a population-based retrospective cohort of patients aged ≥60 years newly prescribed a statin between January 1, 1994, and December 31, 2012, and followed until March 31, 2015, using the UK Clinical Practice Research Datalink. Statins were consecutively classified according to their type, lipophilicity, and potency. For each group, we calculated the crude AD incidence rates per 1,000 person-years. Time-dependent Cox proportional hazards models adjusted for propensity score deciles were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) of incident AD associated with different statin categories.ResultsOver the 18-year study period, we identified 465,085 statin users, including 7,669 patients who developed AD during 2,891,268 person-years of follow-up (incidence rate 2.65 [95% CI 2.59–2.71] per 1,000 person-years). Compared to synthetic, fungus-derived statins were associated with an increased risk of AD (HR 1.09, 95% CI 1.03–1.15). Lipophilic statins also were associated with higher AD risk (HR 1.18, 95% CI 1.09–1.27) compared to hydrophilic statins, while statin potency did not modify the risk of AD (adjusted HR 1.03, 95% CI 0.98–1.08). The risk was further reduced in sensitivity analyses.ConclusionFungus-derived and lipophilic statins were not associated with decreased incidence of AD compared to synthetic and hydrophilic statins. The modest variations in the risk of incident AD observed between statin characteristics needs to be evaluated in future studies on their possible heterogeneous neuroprotective effect.

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