The aims of the study are to evaluate idiopathic normal‐pressure hydrocephalus (INPH)‐related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH ...patients. We investigated cortical CBF utilizing surface‐based early‐phase 18F‐florbetaben (E‐FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three‐dimensional volumetric images, for automated surface‐based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent 18F‐fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age‐ and gender‐matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.
The present study investigates cerebral blood flow (CBF) and cortical thickness using surface‐based analysis of early‐phase 18F‐florbetaben PET and MRI in patients with idiopathic normal‐pressure hydrocephalus (INPH). INPH patients had significantly increased CBF with a concomitant increase in cortical thickness in areas located in the high convexity of the frontal and parietal cortical regions, and significantly decreased CBF without a concomitant change in cortical thickness in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions in comparison to control subjects. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.
Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised ...control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects.
We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER).
Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs.
A better understanding of how drugs work in the real world can complement clinical trials.
The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a ...reduction in the rate of cognitive decline.
To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date.
We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling.
The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2-5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment.
This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.
We assessed the feasibility of plasma Aβ42/Aβ40 determined using a novel liquid chromatography-mass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK ...Study.
A total of 580 participants belonging to six groups, Alzheimer's disease dementia (ADD, n = 134), amnestic mild cognitive impairment (aMCI, n = 212), old controls (OC, n = 149), young controls (YC, n = 15), subcortical vascular cognitive impairment (SVCI, n = 58), and cerebral amyloid angiopathy (CAA, n = 12), were included in this study. Plasma Aβ40 and Aβ42 were quantitated using a new antibody-free, LC-MS, which drastically reduced the sample preparation time and cost. We performed receiver operating characteristic (ROC) analysis to develop the cutoff of Aβ42/Aβ40 and investigated its performance predicting centiloid-based PET positivity (PET+).
Plasma Aβ42/Aβ40 were lower for PET+ individuals in ADD, aMCI, OC, and SVCI (p < 0.001), but not in CAA (p = 0.133). In the group of YC, OC, aMCI, and ADD groups, plasma Aβ42/Aβ40 predicted PET+ with an area under the ROC curve (AUC) of 0.814 at a cutoff of 0.2576. When adding age, APOE4, and diagnosis, the AUC significantly improved to 0.912.
Plasma Aβ42/Aβ40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.
There is a paucity of research regarding the association between the risk of incident dementia and changes in smoking habits in the acute ischemic stroke population. We aimed to investigate the ...effects of smoking habit change on the risk of incident dementia in an ischemic stroke population using data from the Korean National Health Insurance Services Database. This nationwide population-based cohort study included 197,853 patients with ischemic stroke. The patients were divided into never smokers, former smokers, smoking quitters, sustained smokers, and new smokers, based on the 2-year change in smoking status between the two consecutive health examinations before and after the index stroke. The patients were followed up from the index date to 2018 to assess the development of dementia. Dementia was further categorized into Alzheimer's, vascular, and other types of dementia according to the International Classification of Diseases, Tenth Revision diagnosis. Multivariable Cox proportional hazards models were used to assess the association between changes in smoking habits and the risk of dementia. After a median of 4.04 years of follow-up, 19,595 (9.9%) dementia cases were observed. Among them, 15,189 (7.7%) were diagnosed with Alzheimer's disease dementia and 2719 (1.4%) were diagnosed with vascular dementia. After adjusting for covariates, including age, sex, alcohol intake habits, cigarette pack-year, regular physical activity, income, history of hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease, new smokers, sustained smokers, and smoking quitters were significantly associated with a higher risk of all-cause dementia than never smokers (adjusted hazard ratio aHR 1.395, 95% confidence interval CI 1.254-1.552; aHR 1.324, 95% CI 1.236-1.418; and aHR 1.170, 95% CI 1.074-1.275, respectively). Similar trends were observed for both Alzheimer's dementia and vascular dementia, but the association between new smokers and vascular dementia was not significant. The impact of smoking habit change was more prominent in the 40-65-year-old group. New and sustained smokers had a substantially higher risk of incident dementia after ischemic stroke than never smokers. Smoking quitters also had an elevated risk of incident dementia, but the detrimental effects were lower than those in new and sustained smokers.
We aimed to investigate the effects of exercise habit changes on the risk of incident dementia after ischemic stroke using the Korean National Health Insurance Services Database. This study included ...223,426 patients with a new diagnosis of ischemic stroke between 2010 and 2016 who underwent two serial ambulatory health checkups. The participants were divided into four categories according to their habit change or regular exercise: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was new diagnosis of dementia. Multivariate Cox proportional models were used to assess the effects of changes in exercise habits on the risk of incident dementia. After a median of 4.02 years of follow-up, 22,554 (10.09%) dementia cases were observed. After adjusting for covariates, exercise dropouts, new exercisers, and exercise maintainers were significantly associated with a lower risk of incident dementia than persistent non-exercisers (adjusted hazard ratio aHR 0.937; 95% confidence interval CI 0.905-0.970, aHR 0.876; 95% CI 0.843-0.909, aHR 0.705; 95% CI 0.677-0.734, respectively). The impact of changes in exercise habit was more prominent in the 40-65 years age group. An energy expenditure ≥ 1000 metabolic equivalents of task-min/wk post-stroke, regardless of pre-stroke physical activity status, was mostly associated with a lower risk of each outcome. In this retrospective cohort study, initiating or continuing moderate-to-vigorous exercise after ischemic stroke was associated with a lower risk of dementia development. Further, pre-stroke regular physical activity also reduced the risk of incident dementia. The promotion of exercise in ambulatory stroke patients may reduce their future risk of incident dementia.
ObjectiveTo investigate medications associated with cognitive function.DesignPopulation-based cross-sectional cohort study.SettingUK Biobank.ParticipantsUK Biobank participants aged 37–73 years who ...completed cognitive tests at the baseline visit in 2006–2010.Main outcome measuresCognitive test outcomes on verbal–numerical reasoning test (n=165 493), memory test (n=482 766) and reaction time test (n=496 813).ResultsMost drugs (262 of 368) were not associated with any cognitive tests after adjusting for age, gender, education, household income, smoking, alcohol status, psychostimulant/nootropic medication use, assessment centre, and concurrent diagnoses and medications. Drugs used for nervous system disorders were associated with poorer cognitive performance (antiepileptics, eg, topiramate breasoning(score) −0.65 (95% CI −1.05 to −0.24), bmemory(score) −1.41 (−1.79 to −1.04); antipsychotics, eg, risperidone breaction time(ms) −33 (−46 to −20), negative values indicate poor cognitive performance and vice versa). Drugs used for non-nervous system conditions also showed significant negative association with cognitive score, including those where such an association might have been predicted (antihypertensives, eg, amlodipine breasoning −0.1 (−0.15 to −0.06), bmemory −0.08 (−0.13 to −0.03), breaction time −3 (−5 to −2); antidiabetics, eg, insulin breaction time −13 (−17 to −10)) and others where such an association was a surprising observation (proton pump inhibitors, eg, omeprazole breasoning −0.11 (−0.15 to −0.06), bmemory −0.08 (−0.12 to −0.04), breaction time −5 (−6 to −3); laxatives, eg, contact laxatives breaction time −13 (−19 to −8)). Finally, only a few medications and health supplements showed association towards a positive effect on cognitive function (anti-inflammatory agents, eg, ibuprofen breasoning 0.05 (0.02 to 0.08), breaction time 4 (3, 5); glucosamine breasoning 0.09 (0.03 to 0.14), breaction time 5 (3 to 6)).ConclusionsIn this large volunteer study, some commonly prescribed medications were associated with poor cognitive performance. Some associations may reflect underlying diseases for which the medications were prescribed, although the analysis controlled for the possible effect of diagnosis. Other drugs, whose association cannot be linked to the effect of any disease, may need vigilance for their implications in clinical practice.
•Both APOEε4 and hearing impairment (HI) are strong risk factors for dementia.•The relationship between the APOEε4 and HI has been controversial.•The modifying effects of sex on the APOEε4 may have ...contributed to the mixed results.•In our longitudinal setting, male memory clinic visitors with APOEε4 had a higher risk for HI.•Some effects of APOEε4 on dementia may be mediated by HI.
The APOEε4 allele and hearing impairment are risk factors for dementia. Cross-sectional studies have shown controversial findings regarding the relationship between APOEε4 and hearing impairment. These may be explained by reported sex differences in the association between APOEε4 and some Alzheimer's disease biomarkers. We aimed to investigate APOEε4 and hearing impairment in a longitudinal setting considering the modifying effects of sex on APOEε4.
In total, 1810 subjects with APOE genotype at Ilsan Hospital memory clinics were linked to the longitudinal National Health Insurance Service database with International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10) diagnosis codes of hearing impairment. After excluding cases with prevalent hearing impairment and incomplete records, 1092 subjects were analyzed for the period January 2004–July 2019. We used Cox proportional hazard models with or without adjustment for education, hypertension, diabetes, and cognitive function. Effect modification was analyzed by sex stratification and by adding APOEε4 by sex interaction terms.
Hearing impairment did not differ between APOEε4 carriers and non-carriers. Sex-stratification analysis with an unadjusted model showed men with APOEε4 developed more hearing impairment than men without (HR 1.90, 95% CI 1.20–3.01), but women did not. The results remained similar in covariate-adjusted models. The interaction between APOEε4 and sex was also significant regardless of adjustment.
Our longitudinal analyses suggested male memory clinic visitors with APOEε4 allele were more likely to develop hearing impairment than those without the genotype. This group may benefit more from regular monitoring and preventive measures for hearing impairment.
Objectives
As electronic mental health records become more widely available, several approaches have been suggested to automatically extract information from free‐text narrative aiming to support ...epidemiological research and clinical decision‐making. In this paper, we explore extraction of explicit mentions of symptom severity from initial psychiatric evaluation records. We use the data provided by the 2016 CEGS N‐GRID NLP shared task Track 2, which contains 541 records manually annotated for symptom severity according to the Research Domain Criteria.
Methods
We designed and implemented 3 automatic methods: a knowledge‐driven approach relying on local lexicalized rules based on common syntactic patterns in text suggesting positive valence symptoms; a machine learning method using a neural network; and a hybrid approach combining the first 2 methods with a neural network.
Results
The results on an unseen evaluation set of 216 psychiatric evaluation records showed a performance of 80.1% for the rule‐based method, 73.3% for the machine‐learning approach, and 72.0% for the hybrid one.
Conclusions
Although more work is needed to improve the accuracy, the results are encouraging and indicate that automated text mining methods can be used to classify mental health symptom severity from free text psychiatric notes to support epidemiological and clinical research.
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