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

Giorgia Adani,Giovanna Zamboni,Manuela Tondelli,Caterina Garuti,Tommaso Filippini,Chiara Galli,Giulia Vinceti,Manuela Costa,Annalisa Chiari,Marcella Malavolti,Marco Vinceti

doi:10.3390/ijerph17217941

Abstract

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.

Highlights

Early-onset dementia (EOD) is defined by the onset of dementia symptoms before the age of65, regardless of the underlying dementia syndrome
We investigated a wide spectrum of potential environmental risk factors for EOD, some of which, to the best of our knowledge, had not been previously assessed with reference to disease etiology
We found evidence of a beneficial role of educational attainment for EOD prevention, consistent with what has been suggested for late-onset dementia [27]

Summary

Introduction

Early-onset dementia (EOD) is defined by the onset of dementia symptoms before the age of65, regardless of the underlying dementia syndrome. Other genetic risk factors as well as environmental factors might be involved [8], and this may apply to EOD even more than late-onset dementia [9] For this reason, with dementia, as with any other disease, the exposome model assumes an interaction between individual history of exposures and underlying genetic susceptibility of subjects, encompassing the influence of socioeconomic health determinants as well [10]. A recent systematic review about environmental risk factors for dementia, not focused on its early-onset form, found moderate evidence of increased dementia risk associated with environmental and occupational exposure to metals and trace elements, including aluminum, lead and selenium, as well as pesticides and solvents [21]. Long-term use of selenium-containing dietary supplements was associated with increased

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