Age Of Onset In Group Research Articles

Gender differences in major depressive disorder at different ages: a REST-meta-MDD project-based study

BackgroundMajor depressive disorder (MDD) is a highly heterogeneous disease, with differences in clinical manifestations among depression patients based on onset ages and genders. The neural mechanisms underlying these differences remain unclear. In this study, we utilized resting state functional imaging data from a large sample database and adopted the ReHo method to investigate gender differences in local brain function in MDD patients across different onset age groups.MethodsThe study included 364 MDD patients and 695 healthy participants who were part of the REST-meta-MDD project. Regional homogeneity (ReHo) assessed gender disparities in MDD and healthy individuals within groups delineated by gender and onset age (young group: 18–29 years; middle-aged group: 30–45 years).ResultsAmong the young MDD groups, there were significant gender differences in the right superior frontal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and right superior parietal lobule, with male MDD patients having higher ReHo values compared to females. When compared to healthy males, male MDD patients exhibited elevated ReHo values in the right superior parietal lobule. In the middle-aged groups, a marked ReHo difference was observed in the bilateral cerebellum posterior lobe, with female MDD patients showing higher ReHo values.ConclusionsThe functional mechanisms of MDD differ between genders and show distinct variations across different onset age groups. These findings underscore the importance of developing personalized interventions that address the unique needs of MDD patients, tailored to their gender and age, and necessitate the development of antidepressant medications targeted at each gender-age subgroup.

Early onset of hyperuricemia is associated with the risk of nonalcoholic fatty liver disease across life course

Background and aimHyperuricemia is associated with nonalcoholic fatty liver disease (NAFLD), whereas whether the association differed by hyperuricemia onset age remained unclear. This study sought to investigate the associations of hyperuricemia onset age with the risk of incident NAFLD across adulthood. Methods and resultsBased on Kailuan prospective cohort, our analysis comprised 3318 new-onset hyperuricemia cases from 2006 to 2015 and 3318 age- and sex-matched controls who were randomly selected from the general population. The risk of NAFLD across the onset age groups (<45, 45–54, 55–64, and ≥65 years) were compared using multivariable-adjusted Cox regression models. During a median follow-up of 6.78 years, 744 (22.42%) hyperuricemia participants and 586 (17.66%) normouricemia participants were diagnosed with incident NAFLD. After adjusted for potential confounders, the risk of NAFLD was gradually attenuated with each decade increase in hyperuricemia onset age. The adjusted hazard ratio (95% confidence interval) was 1.62 (1.33–1.97) for hyperuricemia onset age <45 years, 1.26 (1.01–1.57) for age of 45–54 years, 1.24 (1.00–1.59) for age of 55–64 years, and 1.19 (0.90–1.71) for age ≥65 years, respectively. The trend remained robust among the multiple sensitivity analyses. ConclusionsThe relative risk of incident NAFLD differed across hyperuricemia onset age-group, and the association was more evident in those with a younger age of hyperuricemia onset, highlighting the importance of performing early strategies on the prevention of NAFLD.

Knowledge of Narcolepsy Among Physicians in Makkah Region, Saudi Arabia: A Cross-Sectional Study.

Background Narcolepsy is a chronic sleep disorder that is characterized by excessive daytime sleepiness and cataplexy. It has been increasingly diagnosed over the years, impacting productivity and employment rates. Awareness of healthcare providers is crucial for the early identification and management of this condition. Objectives This study assessed physicians' knowledge of narcolepsy in the Makkah region of Saudi Arabia. Method This cross-sectional study was conducted from February to November 2023. An online self-administered questionnaire has been used to target physicians working in the Makkah region of Saudi Arabia. The utilized questionnaire assessed demographic and professional data as well as the participants' knowledge of narcolepsy. Statistical analysis was performed using RStudio (R version 4.3.1.). Statistical differences in knowledge were assessed using Pearson's chi-squared and Fisher's exact tests. Factors associated with knowledge of narcolepsy were investigated through univariable and multivariable regression analyses expressed using beta coefficients and 95% confidence intervals (95% CIs). Statistical significance was considered at p < 0.05. Results A total of 226 physicians participated in this study. Male physicians (54.4%, n = 123), practicing in governmental hospitals (77.9%, n = 176) and residing in Makkah City (43.4%, n = 98) were predominant. Non-surgical specialties represented 73.5% (n = 166) of the sample. Around 81% (n = 184) of the participants were aware of narcolepsy, with a significant difference according to professional status (p = 0.045). The majority of physicians have correctly identified narcolepsy as a sleep disorder (78.3%, n = 177), but only 32.3% (n = 73) have identified its typical onset age group and recognized that there are two types of narcolepsy. Almost half of the respondents indicated a lack of knowledge about the diagnostic criteria for narcolepsy in the DSM-5 (52.2%, n = 118). Only 27.4% (n = 62) recognized the correct diagnostic criteria. Half of the sample (51.3%, n = 116) recognized the use of multiple sleep latency tests for the diagnosis. For factors associated with higher participants' knowledge, non-surgical specialties showed significantly higher knowledge scores compared to surgical specialties (beta = 0.91, 95% CI, 0.13 to 1.7, p = 0.024). Conclusion This study has revealed a significant lack of knowledge about narcolepsy among physicians inMakkah region. This raises concerns about the timely identification, proper understanding, and accurate diagnosis of patients with narcolepsy. Adequate understanding of narcolepsy is crucial to avoid its misdiagnosis or delays in receiving appropriate treatment and support, ultimately impacting their quality of life.

Associations between onset age of orthostatic hypotension and incident myocardial infarction, stroke, and dementia: a prospective cohort study.

The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia. Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006-2010) and follow-ups (median=13 years). The propensity score matching method and the Cox proportional hazard models were employed. A total of 448 374 adults (mean age: 56.8±8.1 years), of whom 3795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR=3.15, 95% CI: 2.54 to 3.90, P<0.001), stroke (HR=1.72, 95% CI: 1.33 to 2.23, P<0.001), and dementia (HR=1.26, 95% CI: 1.02 to 1.57, P=0.034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age. Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.

Association Between Onset Age of Coronary Heart Disease and Incident Dementia: A Prospective Cohort Study.

The association of age at coronary heart disease (CHD) onset with incident dementia remains unexplored. This study aimed to examine whether younger onset age of CHD is associated with a higher risk of incident dementia. Data were obtained from the UK Biobank. Information on the diagnosis of CHD and dementia was collected at baseline and follow-ups. Propensity score matching method and Cox proportional hazards models were used to evaluate the association between different ages at CHD onset and incident dementia. A total of 432 667 adults (mean±SD age, 56.9±8.1 years) were included, of whom 11.7% had CHD. Compared with participants without CHD, participants with CHD exhibited higher risks of developing all-cause dementia, Alzheimer's disease, and vascular dementia. More importantly, younger age at CHD onset (per 10-year decrease) was significantly associated with elevated risks of all-cause dementia (hazard ratio [HR], 1.25 [95% CI, 1.20-1.30]; P<0.001), Alzheimer's disease (HR, 1.29 [95% CI, 1.20-1.38]; P<0.001), and vascular dementia (HR, 1.22 [95% CI, 1.13-1.31]; P<0.001). After propensity score matching, patients with CHD had significantly higher risks of all-cause dementia, Alzheimer's disease, and vascular dementia than matched controls among all onset age groups, and the HRs gradually elevated with decreasing age at CHD onset. Younger onset age of CHD is associated with higher risks of incident all-cause dementia, Alzheimer's disease, and vascular dementia, underscoring the necessity to pay attention to the neurocognitive status of individuals diagnosed with CHD at younger age to conduct timely interventions to attenuate subsequent risk of incident dementia.

The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- vs. Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis.

The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to a viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increase MDA5 activity have been associated with an increased risk for immune-mediated diseases, including psoriasis. Our aim is to determine the association between three IFIH1 variants (rs35337543 G/C, intron8 + 1; rs35744605 C/A, Glu627Stop; and rs1990760 C/T, Ala946Thr) and the main clinical findings in a cohort of Spanish patients with psoriasis (N = 572; 77% early-onset). Early-onset psoriasis patients (EOPs) had a significantly higher frequency of severe disease and the Cw6*0602 allele. Carriers of rs1990760 T (946Thr) were more common in the EOPs (p < 0.001), and the effect was more pronounced among Cw6*0602-negatives. This variant was also associated with an increased risk of psoriatic arthritis (PsA) independent from other factors (OR = 1.62, 95%CI = 1.11-2.37). The rs3533754 and rs35744605 polymorphisms did not show significant differences between the two onset age or PsA groups. Compared to the controls, the 946Thr variant was more common in the EOPs (nonsignificant difference) and significantly less common in patients aged >40 years (p = 0.005). In conclusion, the common IFIH1 rs1990760 T allele was significantly more frequent in early-onset compared to late-onset patients. This variant was also an independent risk factor for PsA in our cohort. Our study reinforces the widely reported role of the IFIH1 gene variants on psoriatic disease.

Obsessive-compulsive symptoms in first episode psychosis and risk states: Systematic review with meta-analysis.

Recent studies have reported high prevalences of obsessive-compulsive symptoms and obsessive-compulsive disorder in at risk and first-episode psychosis patients. This sparked an interest in the effect of these symptoms in the clinical characteristics and outcomes of patients. However these studies have never been formally meta-analyzed. Systematic review and meta-analysis of prevalence of obsessive-compulsive symptoms and obsessive-compulsive disorder in at risk and first-episode psychosis patients and comparison of clinical characteristics and outcomes in patients with and without obsessive-compulsive symptoms. Obsessive-compulsive disorder was present in 7.9% (5.9 to 10.0%) and 10.5% (8.3 to 12.8%) and obsessive-compulsive symptoms in 21.4% (8.3 to 38.2%) and 34.0% (26.3 to 42.1%) of at risk and first episode psychosis patients respectively. The prevalences of obsessive-compulsive symptoms had high heterogeneity due in part to different measurement methods and cut-off values. Similar ages of onset for OCS and psychosis symptoms were found (mean difference-0.49years, 95% CI -1.74 to 0.77). Patients with obsessive-compulsive symptoms had statistically insignificant higher Positive and Negative Syndrome Scale (positive subscale) scores and marginally higher depression scores. There were no differences between both groups in age of onset, Positive and Negative Syndrome Scale (negative subscale) score, risk of conversion to psychosis, anxiety score, suicide rate, and functionality score. Obsessive-compulsive disorder and obsessive-compulsive symptoms are very prevalent in at risk and first-episode psychosis patients.

MP41-17 GENOTYPE-PHENOTYPE CORRELATIONS AND CLINICAL OUTCOMES OF VON HIPPEL-LINDAU DISEASE PATIENTS WITH LARGE DELETIONS

You have accessJournal of UrologyCME1 Apr 2023MP41-17 GENOTYPE-PHENOTYPE CORRELATIONS AND CLINICAL OUTCOMES OF VON HIPPEL-LINDAU DISEASE PATIENTS WITH LARGE DELETIONS Kenan Zhang and Kan Gong Kenan ZhangKenan Zhang More articles by this author and Kan GongKan Gong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Approximately 20-40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate genotype-phenotype correlations and clinical outcomes in VHL patients with LDs. METHODS: We included 119 VHL patients from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods in this retrospective study. Other germline mutations were confirmed by Sanger sequencing. Genotype-phenotype correlations and survival were analyzed in different groups using Kaplan-Meier and Cox regression. We also evaluated the therapeutic responses to tyrosine kinase inhibitors (TKIs) therapy. RESULTS: The overall penetrance of patients whose age was <60 was 95.2%. Two VHL patients with LDs also carried CHEK2 and FLCN germline mutations. An earlier age of onset of retinal hemangioblastoma was observed in the next generation. The patients with exon 2 deletion of VHL had an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1 deletion. The earlier onset age group received a poorer prognosis. Four of 8 (50%) patients showed a partial response to TKIs therapy. CONCLUSIONS: The number of generations and the status of exon 2 could affect onset age of VHL-related manifestation. Onset age was an independent risk factor for overall survival. TKIs therapy was effective for VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes. Source of Funding: This work was supported by the National High Level Hospital Clinical Research Funding (High Quality Clinical Research Project of Peking University First Hospital, 2022CR75), National Natural Science Foundation of China (No. 82141103; 82172617; 82172665; 81872081), the Scientific Research Seed Fund of Peking University First Hospital (2021SF01), Capital's Funds for Health Improvement and Research (2022-2-4074), and Sino-Russian Mathematics Center. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e562 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenan Zhang More articles by this author Kan Gong More articles by this author Expand All Advertisement PDF downloadLoading ...

The effect of age at onset of type 1 diabetes mellitus on epilepsy vulnerability

AimsTo examine whether type 1 diabetes age onset correlates with epilepsy incidence. MethodsWe used type 1 diabetes longitudinal data with onset age ≤ 40 years enrolled in Taiwan National Health Insurance program to examine type 1 diabetes onset age effect on epilepsy occurrence. ResultsIn 6,165 type 1 diabetes patients, onset age groups included 3,571 patients (58%) ≤ 18 years (childhood-onset) and 2,594 patients (42%) > 18 years (adulthood-onset). After 8.6 years median follow-up following type 1 diabetes onset, epilepsy incidence rate in adulthood-onset group was 2.26-fold higher than that in childhood-onset group. Epilepsy incidence rate ratio was lowest in those with onset age 6–12 years in comparison to that in patients with onset age ≤ 6 years, but was highest in onset age of 30–40 years. Longer follow-up duration correlates with higher epilepsy risk in adulthood-onset group. Multiple logistic regression analysis showed that onset age 30–40 years, male, more than one diabetic ketoacidosis episode, and unprovoked seizure events were independent risk factors for epilepsy following type 1 diabetes onset. ConclusionsThere is age-related vulnerability to epilepsy following type 1 diabetes onset. Adulthood-onset type 1 diabetes is an independent risk factor for epilepsy susceptibility after type 1 diabetes.

Influence of diabetes mellitus on the biochemical parameters and outcomes of multiple myeloma

ABSTRACTObjective:The incidence of MM in most registries remains stable or showing only a slightly increase. However, prevalence of MM is increasing due to the increase in overall survival in the last two decades. The aim of this study was to observe changes in biochemical parameters during the diagnosis and treatment of MM.Methods:A retrospective analysis was made of the biochemical indicators, survival time, and related adverse events of 196 patients with MM.Results:Of the 196 patients with MM, 26 were diagnosed with DM (DM-MM group) at the first diagnosis, 31 with steroid-induced diabetes mellitus (SID-MM group) during treatment, and 139 without DM (MM group). There was no significant difference between the three groups in the mean age of onset, sex ratio, incidence of hypercalcemia, renal dysfunction, anemia, abnormal lactate dehydrogenase, and median value of D-dimer and fibrinogen during diagnosis and treatment. There was no significant difference in survival time between the SID-MM and MM groups, but there was a significant difference between the DM-MM and MM groups.Conclusion:There was no significant difference between the three groups in the incidence of hypercalcemia, anemia, and renal function impairment. The survival time of patients with DM was shorter than that of patients without DM.

Association of Age of Metabolic Syndrome Onset With Cardiovascular Diseases: The Kailuan Study.

BackgroundMetabolic syndrome (MetS) is associated with an increased risk of incident cardiovascular diseases (CVD), but the association between the new-onset MetS at different ages and the CVD risk remain unclear.MethodsThis was a prospective study comprising a total of 72,986 participants without MetS and CVD who participated in the Kailuan study baseline survey (July 2006 to October 2007). All participants received the biennial follow-up visit until December 31, 2019. In addition, 26,411 patients with new-onset MetS were identified from follow-up, and one control participant was randomly selected for each of them as a match for age ( ± 1 year) and sex. In the end, a total of 25,125 case-control pairs were involved. Moreover, the Cox proportional hazard model was established to calculate the hazard ratios (HR) for incident CVD across the onset age groups.ResultsAccording to the median follow-up for 8.47 years, 2,319 cases of incident CVD occurred. As MetS onset age increased, CVD hazards gradually decreased after adjusting for potential confounders. Compared with non-MetS controls, the HR and the 95% confidence interval (CI) for CVD were 1.84 (1.31–2.57) in the MetS onset age <45 years group, 1.67 (1.42–1.95) for the 45–54 years group, 1.36 (1.18–1.58) for the 55–64 years group, and 1.28 (1.10–1.50) for the ≥65 years group, respectively (p for interaction = 0.03).ConclusionsThe relative risks of CVD differed across MetS onset age groups, and the associations was more intense in the MetS onset group at a younger age.

Factors Associated With Relapse and Treatment of Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease in the United Kingdom

Longer-term outcomes and risk factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well established. To investigate longer-term risk of relapse and factors associated with this risk among patients with MOGAD. This large, single-nation, prospective cohort study was conducted among 276 patients with MOGAD at 5 health care centers in the UK. Data from January 1973 to March 2020 were collected from 146 patients at Oxford and its outreach sites, 65 patients at Liverpool, 32 patients at a children's hospital in Birmingham, 22 patients at a children's hospital in London, and 11 patients at Cardiff, Wales. Data were analyzed from April through July 2020. Risk of relapse and annualized relapse rate were evaluated according to different baseline features, including onset age, onset phenotype, and incident vs nonincident group, with the incident group defined as patients diagnosed with antibodies against myelin oligodendrocyte glycoprotein before a second attack. Time to next relapse among patients experiencing relapse was measured and compared between the maintenance therapy subgroup and each first-line treatment group. The no-treatment group was defined as the off-treatment phase among patients who were relapsing, which could occur between any attack or between the last attack and last follow-up. Among 276 patients with MOGAD, 183 patients were identified as being part of the incident group. There were no differences in mean (SD) onset age between total and incident groups (26.4 [17.6] years vs 28.2 [18.1] years), and female patients were predominant in both groups (166 [60.1%] female patients vs 106 [57.9%] female patients). The most common presentation overall was optic neuritis (ON) (119 patients among 275 patients with presentation data [43.3%]), while acute disseminated encephalomyelitis (ADEM), brain, or brainstem onset was predominant among 69 patients aged younger than 12 years (47 patients [68.1%]), including 41 patients with ADEM (59.4%). In the incident group, the 8-year risk of relapse was 36.3% (95% CI, 27.1%-47.5%). ON at onset was associated with increased risk of relapse compared with transverse myelitis at onset (hazard ratio [HR], 2.66; 95% CI, 1.01-6.98; P = .047), but there was no statistically significant difference with adjustment for a follow-on course of corticosteroids. Any TM at onset (ie, alone or in combination with other presentations [ie, ON or ADEM, brain, or brain stem]) was associated with decreased risk of relapse compared with no TM (HR, 0.41; 95% CI, 0.20-0.88; P = .01). Young adult age (ie, ages >18-40 years) was associated with increased risk of relapse compared with older adult age (ie, ages >40 years) (HR, 2.71; 95% CI, 1.18-6.19; P = .02). First-line maintenance therapy was associated with decreased risk of relapse when adjusted for covariates (prednisolone: HR, 0.33; 95% CI, 0.12-0.92; P = .03; prednisolone, nonsteroidal immunosuppressant, or combined: HR, 0.51; 95% CI, 0.28-0.92; P = .03) compared with the no-treatment group. The findings of this cohort study suggest that onset age and onset phenotype should be considered when assessing subsequent relapse risk and that among patients experiencing relapse, prednisolone, first-line immunosuppression, or a combination of those treatments may be associated with decreased risk of future relapse by approximately 2-fold. These results may contribute to individualized treatment decisions.

Study of Clinical Features and Diagnosis Pattern of Duchene Muscular Dystrophy in Southern India.

Background Duchene muscular dystrophy (DMD) is an X-linked progressive muscle disorder that is characterized by proximal muscle weakness followed by a premature death in young boys. There is a low index of reports on diagnosis ratio and clinical features in Southern India. Objective The present study aimed to conduct an observational survey on preliminary analysis, family history, associated complaints, and diagnosis ratio of DMD in southern regions of India. Materials and Methods A systematic observation and survey were conducted on clinically confirmed DMD patients registered between 2019 and 2021 through the questionnaire. The questionnaire and pattern of study were identified by exploring published and unpublished studies available from electronic databases and critical assessment criteria considered by physicians. Preliminary analysis such as onset criteria, motor difficulties, milestone delay; family history and consanguinity analysis; chief complaints (ambulatory status, lordosis, respiratory, and cardiac outcomes), associated complaints such as enlarged tongue, oral hygiene, behavioral problems; and other similar parameters were studied. An assessment of the diagnosis rate and pattern was performed. Statistical analysis The data were reviewed and interpreted through statistical methods mean ± standard deviation represented as a percentage. Results In total, 400 DMD patients were included and 250 participated in the study. The onset age group was 2 to 5 years in 37% of the population. Milestone delay was seen in 86%; consanguinity marriage of parents was reported in 39%. Frequent falls were reported in 62% in 5 to 8 years old group. Wheelchair status was reported in 65% in 9 to 12 years old. Cervical and lumbar lordoses were seen in 57 and 69%, respectively, in above 13 years old. Respiratory and cardiac complications were 88 and 78% reported in above 13 years old, respectively. Other major associated complaints such as enlarged tongue were reported in 79%. Fifty-one percent underwent genetic diagnosis and 79% of the population underwent serum creatine phosphokinase (CPK) analysis for the confirmation of DMD. Conclusion In this study population of South India, milestone delay was a major observation. Although there was a slight margin, family history shows “no blood relation among parents” in the majority of the study population. Chief complaints were predominantly severe above 13-year age group population. Serum CPK was the first choice for the first investigation, which is followed by a genetic diagnosis.

Relationship of APOE, age, amyloid and clinical phenotype in Alzheimer disease

AbstractBackgroundThe apolipoprotein ε4 (APOE4) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationships between APOE genotype and age, amyloid‐beta (Aβ) deposition and clinical phenotype in Alzheimer’s disease.Method138 atypical AD patients (57 posterior cortical atrophy and 81 logopenic aphasia) were recruited by the Neurodegenerative Research Group at Mayo Clinic, and underwent APOE testing and Pittsburgh Compound B PET. 318 typical AD patients with APOE genotype and known onset age were identified from ADNI (121 had Aβ‐PET). Aβ‐PET was quantified using the centiloid scale. Logistic regression was used to estimate the proportion of APOE4 carriers by onset age and clinical group. Linear regression was used to estimate mean Aβ centiloid by age, APOE4 status, and clinical group in patients who were Aβ‐positive (centiloid≥19).ResultThe overall frequency of APOE4 carriers was lower in atypical AD (52%) compared to typical AD (66%), particularly for ε4ε4 homozygotes (9% vs 20%). APOE4 frequency increased with age in atypical AD, but showed a bell‐shaped curve in typical AD where highest frequencies were observed between 65‐70 years (Figure). Typical AD showed higher APOE4 frequencies than atypical AD only between the ages of 57 and 69 years. Aβ centiloid was higher in atypical AD compared to typical AD by approximately 16 centiloid units, but did not differ according to APOE4 status (Figure). Aβ centiloid stayed relatively flat with increasing age for both carriers and non‐carriers in atypical AD, but declines with increasing age in typical AD. Relationships between APOE4 and age, as well as centiloid, did not differ between the two atypical AD phenotypes.ConclusionAPOE4 frequency differs between atypical and typical AD but is highly dependent upon age, with higher APOE4 frequency in typical AD only observed between 57 and 69 years. The findings highlight the importance of age and clinical phenotype in understanding the effects of APOE genotype in Alzheimer’s disease.

Colorectal cancer patients in a tertiary hospital in Indonesia: Prevalence of the younger population and associated factors

BACKGROUNDAn increasing trend in colorectal cancer (CRC) occurring at younger ages has been observed worldwide, even though incidence is declining in the general population. Most currently available guidelines still recommend CRC screening for older populations, despite an alarming rise in early-onset CRC incidence. Risk stratification is necessary to further determine the population most at risk for early-onset CRC. However, epidemiological data on related clinical characteristics and potential risk factors, especially in developing countries, have not been widely reported.AIMTo investigate the prevalence, demographics, clinicopathologic features, and associated factors of young-onset CRC patients in a tertiary hospital in Indonesia.METHODSPatients undergoing colonoscopy examination between 2008 and 2019, yielding a diagnosis of CRC were identified from medical records. The subjects were classified into two groups according to their age at diagnosis, namely early-onset (18-49 years old) and late-onset (≥ 50-years-old). Demographic data, characteristics, and risk factors of both onset age groups were evaluated using the chi-square and Fisher’s exact test.RESULTSAmong 495 CRC patients confirmed by histopathology, 205 (41.4%) were classified as early-onset and 290 (58.6%) as late-onset. Most subjects in the early-onset CRC group were male (53.7%), with 89.8% displaying adenocarcinoma histopathology. A majority (78%) of the early-onset CRC patients had left-sided tumors, with the rectum (41%) and rectosigmoid (17.6%) being the most common sites. Abdominal pain was the most frequent symptom in the early-onset CRC patients (55.6%), which was significantly higher than that in the late-onset CRC patients (43.8%, P < 0.05). Early-onset CRC cases were more likely to be underweight (34.6% vs 20.0%, P < 0.001) compared to late-onset CRC cases. The proportion of subjects with suspected hereditary nonpolyposis colorectal cancer (HNPCC) was also higher in the early-onset CRC group than in the late-onset age group (9.3% vs 4.1%, P < 0.05). However, no difference was observed in the parental or family histories of CRC cases.CONCLUSIONEarly-onset CRC patients were more likely to have abdominal pain, underweight status, and HNPCC suspicion than late-onset CRC patients.

Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome.

Adults with Down syndrome (DS) have an exceptionally high frequency of Alzheimer disease (AD) with a wide variability in onset, from 40 to 70 years of age. Equally prevalent in DS is hypothyroidism. In this study, we sought to quantify the relationship between the two. A total of 232 adults with DS and AD were stratified into three AD onset age groups: early (<47 years), typical (48–59), and late (>59). Among patients with available data, differences in the distributions of demographics, hypothyroidism variables (presence, age of onset), thyroid function tests, thyroid autoantibodies, and APOE genotypes were assessed (e.g., chi-squared, Mann–Whitney tests). Spearman and partial Spearman correlations and ordinal logistic regression models were constructed to quantify the association between ages of AD and hypothyroidism onset with and without covariate adjustments. We observed a positive association between the ages of AD and hypothyroidism onset after accounting for APOE-Ɛ4 (correlation: 0.44, 0.24, 0.60; odds ratio: 1.09, 1.05–1.14). However, an early age of hypothyroidism onset and the presence of the APOE-Ɛ4 allele were independently associated with the early age of AD onset. Similar findings were observed when accounting for other factors. Our study provides evidence for the importance of hypothyroidism and associated pathological mechanisms for risk of AD in DS.

Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study.

OBJECTIVEWe aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in the Chinese population.RESEARCH DESIGN AND METHODSThis study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2017. During follow-up, 11,384 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% CIs of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus control subjects across age-groups.ResultsDuring a median follow-up of 5.57 years, 1,794 incident events (907 CVD events, of which there were 725 strokes and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age <45 years had the highest relative risks of CVD and all-cause mortality relative to the matched control subjects, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age.CONCLUSIONSThe relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age-groups, and the associations were more evident in younger-onset type 2 diabetes.

A26 A SYSTEMTIC REVIEW OF MONOGENIC INFLAMMATORY BOWEL DISEASE: CLINICAL PHENOTYPE AND GENOTYPE

Abstract Background Advances in genomic technologies have led to an increase in reports of monogenic inflammatory bowel disease (IBD). The majority of the studies on monogenic IBD have focused only on young children aged &amp;lt;6 years. There are no detailed reports containing a comprehensive picture of monogenic IBD with specific numbers on the clinical features, genetic profiles and disease course. Since each gene-specific cause of monogenic IBD is rare, it is difficult to collect cases in a single study even with international cohort studies. Aims To elucidate a comprehensive picture of monogenic IBD, we conducted a systematic review of all reported cases of monogenic IBD. Methods A systematic review of MEDLINE articles published between January 2000 and December 2019 was conducted. 662 monogenic IBD cases were identified from 273 eligible articles. Data on clinical manifestation, genotype, and management were collected. Results The most frequently reported genes causative of monogenic IBD patients were IL10RA, CYBB, IL10RB, and TTC7A (Figure). In total, 64.8% of patients developed IBD before six years old, 15.6% between ages 10 and 17.9 years, and 11.6% at age 18 years or older. Only 32.7% had any history of extra-intestinal manifestation (EIM) before IBD onset. There was substantial difference in the onset age groups and the underlying monogenic disorders. 74.4% developed at least one EIM during their clinical course. The most common EIMs were atypical infection (44.1%), dermatologic abnormality (39.2%), autoimmunity (22.7%) and lymphoid organ abnormality (11.5%). Autosomal recessive (62.8%) was the most common inheritance pattern, and missense-variants (44.3%) were the most identified type of genetic variants. Deletions including CNVs, intronic, synonymous and inversion, which have the possibility to be overlooked by whole exome sequencing were shown in some cases. Bowel surgery, biologics, and hematopoietic stem cell transplantation were performed in 28.3%, 32.8%, and 24.4% of patients, respectively. Conclusions Monogenic IBD diagnosis and management is a challenging clinical problem across age groups; the EIMs are more diverse and the management is evidently more difficult compared to non-monogenic IBD. An improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is necessary for effective management. Funding Agencies CAG, CIHRUehara Memorial Foundation Fellowship

Very High Incidence of Type 1 Diabetes Among Children Aged Under 15 Years in Tlemcen, Northwest Algeria (2015-2018)

Objective:In Algeria, there is a lack of epidemiological data concerning childhood type 1 diabetes (T1D). The International Diabetes Federation estimated in 2019 that Algeria ranked 7th among countries with the highest prevalence of T1D. This study aimed to determine the incidence of T1D in children <15 years, living in Tlemcen in Northwest Algeria.Methods:A retrospective study using data from children (<15 years) who have been diagnosed with T1D in Tlemcen between 2015 and 2018, using the two-source capture–recapture method to estimate the completeness of ascertainment (%). Total average incidences, by sex, by onset age group, and by season of onset were calculated per 100,000 and per year.Results:During the study period, 437 new cases of T1D were registered, among them, 233 boys and 204 girls, with a sex ratio of 1.14. The average annual incidence rate of childhood T1D was 38.5/100,000 with a 95% confidence interval (CI): 35.20-41.79; boys: 40.51, 95% CI: 38.16-42.85; girls: 36.49, 95% CI: 34.17-38.80. Overall incidence rates in 2015, 2016, 2017 and 2018 were respectively 36.6 (95% CI: 33.72-39.48), 38.7 (95% CI: 35.43-41.97), 39.3 (95% CI: 35.97-42.62) and 39.5 (95% CI: 36.12-42.87)/100,000. Newly diagnosed children were more likely to present in winter and autumn. Ketoacidosis at diagnosis was diagnosed in 29.2%.Conclusion:The mean incidence of childhood T1D in Tlemcen was 38.5/100,000, this incidence is in the “extremely high” category of the World Health Organization DiaMond project classification of diabetes giving this region a very high risk.

Comparing the onset of child sexual abuse perpetration from adolescence into adulthood: Are there unique risks, and what does this mean for prevention?

BackgroundThere are no known studies that have directly compared factors associated with the onset of child sexual abuse (CSA) perpetration during emerging adulthood, with CSA perpetration in other life-stages. ObjectiveThis study investigated common and distinct factors associated with the onset of CSA perpetration (i.e., age at first child sexual offense) across the life course to inform, and tailor, current prevention efforts. Participants and settingThe sample comprised 354 males, from custodial and community corrections, and sentenced for sexual offenses against children. MethodsUsing self-report and official data, the sample was stratified into three age groups: adolescence (n = 214; 10–17 years), emerging adulthood (n = 39; 18−25 years) and later adulthood (n = 101; 26+ years). Bivariate analyses were conducted to compare developmental and contextual factors associated with CSA perpetration. A multinomial logistic regression was then performed to examine distinct risk factors for CSA-onset in emerging adulthood, compared to the other onset age groups. ResultsBivariate analyses identified similarities and differences among the groups. The multinomial regression identified several factors distinguishing the emerging-adulthood group from the adolescence and later-adulthood onset groups. The combined results point to some notable differences in the emerging-adulthood group, including the disproportionate number of offenses perpetrated against male children, strangers, and in public. ConclusionsImplications for existing prevention and rehabilitation strategies are discussed in light of these findings, especially the need for a developmental lens to prevention and intervention efforts. Research to further delineate risks unique to onset of CSA in emerging adulthood is also warranted.