Environmental and occupational risk factors for early onset dementia in an Italian community

Background: Early onset dementia (EOD) is defined as dementia with symptoms onset before 65 years. Little is known about the etiological role of environmental and occupational risk factors. We aimed at assessing the role of these factors in disease etiology.Methods: Using a case-control design, we recruited all EOD cases resident in Modena province from October, 2016 to October, 2019, as well as a referent population drawn from patients’ care-givers. We investigated residential history of study participants, and their occupational and environmental exposures to pesticides, solvents and metals through a self-administered questionnaire. We computed the odds ratios (ORs) of disease risk, and the corresponding 95% confidence intervals (CIs), according to exposure to the investigated risk factors, using an unconditional logistic regression model adjusted for sex, age, and education. Results: Fifty-eight EOD cases and fifty-four controls agreed to participate. Among occupational factors, disease risk was associated with exposure to aluminum (OR 2.6, 95% CI 0.4-15.7), pesticides (OR 2.3, 95% CI 0.7-7.8) particularly from agricultural occupational exposure (OR 3.1, 95% CI 0.7-13.3) and dyes, paints or thinners (OR 1.7, 95% CI 0.6-5.0). Among lifestyles factors, smoking (OR 1.3, 95% CI 0.6-2.9) and playing football (OR 2.2, 95% CI 0.5-9.3) or cycling (OR 2.3, 95% CI 0.4-13.4) were associated with higher EOD risk, although overall sports practice appeared to be protective factor (OR 0.4, 95% CI 0.2-0.9). Risk was also positively associated with history of head trauma (OR 1.2, 95% CI 0.3-4.1) and particularly upper arm trauma (OR 2.2, 95% CI 0.7-7.5), but not overall trauma. No association emerged for exposure to electromagnetic fields. Conclusions:Despite the study limitations, our results appear to support a role of environmental risk factors in EOD etiology, particularly of some chemical exposures and professional sports, while overall sports practice may have a beneficial effect

Environmental Risk Factors for Early-Onset Alzheimer's Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy

Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases' caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer's dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk

Epidemiology and social impact of early onset dementia in the province of Modena, Northern Italy

Aims of the study. Early onset dementia (EOD), defined as onset of dementia <65 years, has a much higher social impact compared to the more common late onset dementia. EOD epidemiologic data in Italy are extremely scarce, and international estimates of prevalence are considerably variable, ranging between 15.1 and 153/100.000 in the age 45-65. We present data from an ongoing study aimed at establishing EOD epidemiology in a Northern Italy community (Modena province, around 700.000 inhabitants). Materials. We retrospectively recruited all patients residing in Modena province referred to the Modena Baggiovara Hospital Neurologic Clinic CDCD (Centro disturbi cognitivi e demenze), by family practitioners and geriatricians of the province. Eligible patients were those affected by EOD from 2012 to January 2019. EOD was diagnosed in patients <65 years presenting with cognitive/behavioral symptoms, following a comprehensive neurological examination by a cognitive neurologist, as well as brain MRI, FDG PET scanning and CSF analyses when appropriate. Methods. We collected clinical data such as age at onset, disease severity at time of diagnosis, time delay from onset to diagnosis, and epidemiologic data including residence and occupational status. Results. We identified 223 patients with an EOD diagnosis from 2012 to January 2019. Of these, 103 are males (46,2%). 97 patients have AD (21 lvPPA, 13 PCA, 2 frontal variant), 47 have FTD (33 bvFTD, 14 svPPA), 6 have leucoencephalopathy. Mean onset age was 58,6 years (SD 5,1). Median time from symptoms onset to diagnosis was 3.1 years (SD 29,83). Mean MMSE score at diagnosis was 22,63/30 (SD 5,2). 24 patients were working at time of diagnosis (10,76%) and had to quit working due to the cognitive impairment. Two patients (0,89%) had young children (<18) at time of diagnosis. Discussion. We provide the first epidemiological data on EOD in Italy. These are consistent with the estimates calculated by transposing European data to the population of Modena province (estimated prevalence=200 patients, detected prevalence=223 patients)1. Our data show a higher percentage of atypical AD phenotypes and FTD in the EOD group compared to late onset disease2. Also, CAA and leucoencephalopaties were over-represented compared to LOD. From a social perspective, EOD has significant impacts on patients and their families: patients are generally forced to leave work, and their children are expected to need psychological support, currently not routinely available. Conclusions. Our population study provides the first data regarding EOD epidemiology and social impact in Italy

Plasma Cell-Free DNA Integrity Assessed by Automated Electrophoresis Predicts the Achievement of Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

PURPOSE The study of plasma cell-free DNA integrity (cfDI) has shown potential for providing useful information in neoplastic patients. The aim of this study is to estimate the accuracy of an electrophoresis-based method for cfDI evaluation in the assessment of pathologic complete response (pCR) in patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT). PATIENTS AND METHODS Fifty-one patients with BC undergoing anthracycline-/taxane-based NACT were recruited. Plasma samples were collected from each patient at diagnosis (t0), after anthracycline administration (t1), and after NACT completion (t2). The concentration of differently sized cell-free DNA fragments was assessed by automated electrophoresis. cfDI, expressed as cfDI index, was calculated as the ratio of 321-1,000 bp sized fragment concentration to 150-220 bp sized fragment concentration assessed at t2. cfDI index was then used to build an exploratory classifier for BC response to NACT, directly comparing its sensitivity and specificity with magnetic resonance imaging (MRI), through bootstrapped logistic regression. RESULTS cfDI index was assessed on 38 plasma samples collected from as many patients at t2, maintaining a 30/70 ratio between pCR and non-pCR patients. cfDI index showed an area under the receiver operating characteristic curve in predicting the achievement of pCR of 81.6, with a cutoff above 2.71 showing sensitivity = 81.8 and specificity = 81.5. The combination of cfDI index and MRI showed, in case of concordance, an area under the receiver operating characteristic curve of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7. CONCLUSION cfDI index measured after NACT completion shows great potential in the assessment of pCR in patients with BC. The evaluation of its use in combination with MRI is strongly warranted in prospective studies

Primary and secondary prevention to effectively reduce the risk of bisphosphonate-related osteonecrosis of the jaw in patients with bone metastases .

Background Bone is one of the most frequent sites of metastasis in patients with advanced cancer. Nearly all patients with myeloma, 65–75% of patients with prostate or breast cancer, and 30–40% of patients with lung cancer or other solid tumors, eventually develop bone metastases. Bisphosphonates (BP), particularly zoledronic acid and denosumab, were demonstrated to effectively reduce skeletal complications in patients with bone metastases. However, bisphosphonate-related osteonecrosis of the jaw (BRONJ) can occur spontaneously, favored by dental extraction, dental implant surgery, or denture wearing. The purpose of this study was to underline the role of dental prevention as an effective tool to reduce the risk of BRONJ. Material and methods BRONJ was identified with the standardized query “osteonecrosis” among all data from patients treated at Modena Cancer Center from 2005 to 2016. For each case, demographic and medical information were analyzed, as well as data about notification (year of occurrence, outcome), type and duration of BP exposure, and associated risk factors (dento-alveolar surgery, chemotherapy, antiangiogenics). Data were differently analyzed taking into account the implementation of a Dental Prevention Service in patients who are candidates for BP therapy.Results Among 1663 patients treated with BP, 63 cases of BRONJ were identified (3.8%). 44 female and 19 men with a median age of 69 years (range 47-90 years), have been treated with BP for bone metastases from breast cancer (54%), hematologic malignancy (21%), prostate cancer (13%), renal cancer (5%), lung cancer (2%) and other tumors (5%). 15 maxillae and 48 mandibles were involved. The trigger event was a dental extraction in 29% of the cases, being spontaneously the other 71%. The median time to BRONJ was 28 months (range 1-89.1 months) from the first dose of BP, and 25 was the mean number of BP doses administered before BRONJ. Overall, a preliminary odontoiatric evaluation was performed in only 14 cases (22%). All but one of these dentistry opinions were obtained after 2010 when the Dental Prevention Service was created, which is a drop out of the risk of BRONJ from 4.1 to 1.9%. Conclusions. Prevention of the BRONJ is critical in in bone metastatic patients. The incidence of BRONJ over time can drop to 1.9% when primary and secondary prevention measures are implemented in routine clinical practice

Labile plasma iron and echocardiographic parameters are associated to cardiac events in beta-thalassemic patients

Background and aim: Notwithstanding the improvement in therapies, patients affected by thalassemia major (TM) and intermedia (TI) are still at high risk of cardiac complications. This study aimed at evaluating the incidence and predictive factors for developing cardiac events in adult β-TM and TI patients. Population andmethods: Data on diagnosis and clinical historywere collected retrospectively; prospective data on new-onset cardiac failure and arrhythmias, echocardiographic parameters, biochemical variables including non-transferrin-bound iron (NTBI) and labile plasma iron (LPI), magnetic resonance imaging (MRI) T2* measurement of hepatic and cardiac iron deposits, and iron chelation therapy were recorded during a 6 year follow-up. Results: Thirty-seven patients, 29 TM and 8 TI, were included. At baseline, 8 TM patients and 1 TI patient had previously experienced a cardiac event (mainly heart failure). All patients were on chelation therapy and only 3 TM patients had mild-to-severe cardiac siderosis. During follow-up, 11 patients (29.7%) experienced a new cardiac event. The occurrence of cardiac events was correlated to high LPI levels (OR 12.0, 95% CI 1.56-92.3, p 0.017), low mean pre-transfusion hemoglobin (OR 0.21, 95% C.I. 0.051-0.761, p 0.21), and echocardiographic parameters suggestive of myocardial hypertrophy. Multivariate analysis disclosed high LPI and left ventricle mass index (LVMI) as independent variables significantly associated with cardiac events. Cardiac iron deposits measured by MRI T2* failed to predict cardiac events. Conclusion: LPI, Hb levels, and echocardiographic parameters assessing cardiac remodeling are associated to cardiac events in adult TM and TI patients. LPI might represent both a prognostic marker and a potential target for novel treatment strategies. Further studies are warranted to confirm our findings on larger population

Atrial Fibrillation and Other Cardiovascular Factors and the Risk of Dementia: An Italian Case–Control Study

: Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case-control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016-2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32-11.28, and 3.64; 95% CI 0.32-41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD

Outdoor artificial light at night and risk of early-onset dementia: A case-control study in the Modena population, Northern Italy

Background Dementia is a neurological syndrome characterized by severe cognitive impairment with functional impact on everyday life. It can be classified as young onset dementia (EOD) in case of symptom onset before 65, and late onset dementia (LOD). The purpose of this study is to assess the risk of dementia due to light pollution, and specifically outdoor artificial light at night (LAN). Methods Using a case-control design, we enrolled dementia patients newly-diagnosed in the province of Modena in the period 2017–2019 and a referent population from their caregivers. We geo-referenced the address of residence on the date of recruitment, provided it was stable for the previous five years. We assessed LAN exposure through 2015 nighttime luminance satellite images from the Visible Infrared Imaging Radiometer Suite (VIIRS). Using a logistic regression model adjusted for age, sex, and education, we calculated the risk of dementia associated with increasing LAN exposure, namely using <10 nW/cm2/sr as reference and considering ≥10-<40 nW/cm2/sr intermediate and ≥40 nW/cm2/sr high exposure, respectively We also implemented non-linear assessment using a spline regression model. Results We recruited 58 EOD cases, 34 LOD cases and 54 controls. Average LAN exposure levels overlapped for EOD cases and controls, while LOD cases showed higher levels. Compared with the lowest exposure, the risk of EOD associated with LAN was higher in the intermediate exposure (OR = 1.36, 95% CI 0.54–3.39), but not in the high exposure category (OR = 1.04, 95% CI 0.32–3.34). In contrast, the risk of LOD was positively associated with LAN exposure, with ORs of 2.58 (95% CI 0.26–25.97) and 3.50 (95% CI 0.32–38.87) in the intermediate and high exposure categories, respectively. The spline regression analysis showed substantial lack of association between LAN and EOD, while almost linear although highly imprecise association emerged for LOD. Conclusions Although the precision of the estimates was affected by the limited sample size and the study design did not allow us to exclude the presence of residual confounding, these results suggest a possible role of LAN in the etiology of dementia, particularly of its late-onset form