Background and aim: Dementia is a progressive neurodegenerative disease generally affecting subjects in the elderly. However, it may occur also at younger age before 65 years, yielding a condition called early-onset dementia (EOD). In recent years both prevalence and incidence of EOD has increased, including in Italy. Apart identification of few genetic factors, the etiology of dementia is largely unknown. This study aims at evaluating the role of environmental factors on the risk of Alzheimer’s dementia with early onset and other neurodegenerative diseases in a population of Modena in Emilia-Romagna region, Italy. Methods: Using a case-control design, we identified newly-diagnosed EOD cases in the period 2016-2019 in Modena province, while referent population were recruited from caregivers of subjects with dementia. We investigated factors related to environmental exposure, occupational activities, and dietary habits through two tailored questionnaires. The first one collected information about personal characteristics, clinical and family history of diseases and comorbidities, occupational history, hobbies and other leisure activities, residential history, and domestic use of pesticides. We also assessed EOD risk for exposure to light-at-night (LAN) using satellite data into a geographical information system. Finally, we assessed dietary habits by administrating a validated semi-quantitative food frequency questionnaire specifically developed for Northern Italian population evaluating adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. Results: We eventually recruited 58 EOD cases (32 with Alzheimer’s dementia and 19 with fronto-temporal dementia) and 54 controls. 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. About LAN exposure, we found an increase in risk at intermediate exposure categories, though further higher levels of LAN did not show similar OR increase. Finally concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Mediterranean and DASH diets emerged only at very high adherence levels. Conclusions: Our study evaluated possible environmental and occupational risk factors for EOD in Modena population. About clinical history, previous head trauma, atrial fibrillation, stroke, diabetes or dyslipidemia have been positively associated EOD risk. Regarding occupational factors, our findings suggest that use of pesticides, dyes/paints, and metalloids such as aluminum and selenium could be associated with increased disease risk, while no clear association emerged for environmental or residential risk factors including LAN exposure, with the exception of a higher risk associated with smoking. Finally, the association between dietary factors and EOD suggests that adherence to the MIND dietary pattern may linearly decrease such risk. Despite study limitations due to case-control design, including possible occurrence of selection and recall bias but likely to a limited extent, our findings highlighted a possible role of some environmental and lifestyle risk factors in the etiology of young-onset dementia.

Introduzione e scopo: La demenza è una malattia neurodegenerativa progressiva che colpisce generalmente soggetti anziani ma in caso di esordio dei sintomi in età più giovane prima dei 65 anni, si parla di demenza ad esordio precoce (EOD), una condizione in aumento sia in prevalenza che incidenza anche in Italia. A parte l'identificazione di alcuni fattori genetici, l'eziologia della demenza è in gran parte sconosciuta. Questo studio mira a valutare il ruolo dei fattori ambientali sul rischio di EOD in una popolazione italiana dell’Emilia Romagna. Metodi: Utilizzando un disegno caso-controllo, abbiamo identificato casi di EOD di nuova diagnosi nel periodo 2016-2019 nella provincia di Modena, e come controlli i caregivers di soggetti affetti da demenza. Abbiamo studiato i fattori legati ad esposizione ambientale, attività lavorativa e abitudini alimentari attraverso due questionari predisposti ad hoc. Il primo ha raccolto informazioni su caratteristiche personali, anamnesi familiare e patologica, storia professionale, hobby e tempo libero, storia residenziale e uso domestico di pesticidi. Abbiamo inoltre valutato il rischio di EOD per l'esposizione alla luminanza notturna (LAN) tramite il ricorso a dati satellitari. Infine, abbiamo valutato le abitudini alimentari somministrando un questionario validato semi-quantitativo sulla frequenza alimentare sviluppato specificamente per la popolazione dell'Italia settentrionale valutando l'aderenza ai pattern dietetici, tra cui l’indice Greco-Mediterraneo, il Dietary Approaches to Stop Hypertension (DASH) e Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND). Risultati: In totale abbiamo reclutato 58 casi di EOD (32 con demenza di Alzheimer e 19 con demenza fronto-temporale) e 54 controlli. La maggior parte delle esposizioni studiate, come l'esposizione professionale ad alluminio, pesticidi, coloranti, vernici o diluenti, erano associate a un aumento dell'odds ratio (OR) per FTD ma non per AD. L'uso a lungo termine di integratori alimentari contenenti selenio è stato associato ad un aumento dell'OR per EOD e, in particolare, per FTD. Per entrambe le forme di EOD, fumare e giocare a calcio hanno mostrato un aumento dell'OR, mentre il ciclismo è stato associato a un aumento del rischio solo nell'FTD. La pratica sportiva complessiva sembrava essere un fattore protettivo per entrambi i tipi. Per quanto riguarda l'esposizione LAN, abbiamo riscontrato un aumento del rischio nelle categorie di esposizione intermedie, sebbene ulteriori livelli più elevati di LAN non abbiano mostrato un aumento di OR simile. Infine, per quanto riguarda i pattern dietetici, il rischio di EOD risulta diminuito linearmente con la crescente aderenza alla dieta MIND. Un'associazione inversa per le diete mediterranea e DASH è invece emersa solo a livelli di aderenza molto elevati. Conclusioni: Il nostro studio ha valutato possibili fattori di rischio ambientali e occupazionali per il rischio di EOD nella popolazione modenese. Per quanto riguarda la storia clinica, precedenti traumi cranici e fibrillazione atriale presentano una associazione positiva. Sui fattori occupazionali, i nostri risultati suggeriscono che l'uso di pesticidi, coloranti/vernici e metalloidi come alluminio e selenio potrebbe essere associato ad un aumento del rischio di malattia, mentre non è emersa alcuna chiara associazione per fattori ambientali o residenziali, inclusa l'esposizione alla LAN, con l'eccezione di un rischio maggiore associato al fumo. Infine, i dati sui fattori dietetici suggeriscono che l'adesione al pattern MIND possa diminuire il rischio di EOD in modo lineare. Nonostante i limiti dello studio dovuti al disegno caso-controllo e alla possibile occorrenza, seppur in modo presumibilmente limitato, di distorsioni di selezione e misura, i nostri risultati evidenziano un possibile ruolo di alcuni fattori ambientali e di stile di vita nell'eziologia della demenza a esordio giovanile.

Studio dei determinanti ambientali e comportamentali della demenza di Alzheimer ad esordio precoce ed altre patologie neurodegenerative: uno studio caso controllo in Italia / Tommaso Filippini , 2022 May 27. 34. ciclo, Anno Accademico 2020/2021.

Studio dei determinanti ambientali e comportamentali della demenza di Alzheimer ad esordio precoce ed altre patologie neurodegenerative: uno studio caso controllo in Italia

FILIPPINI, TOMMASO
2022

Abstract

Background and aim: Dementia is a progressive neurodegenerative disease generally affecting subjects in the elderly. However, it may occur also at younger age before 65 years, yielding a condition called early-onset dementia (EOD). In recent years both prevalence and incidence of EOD has increased, including in Italy. Apart identification of few genetic factors, the etiology of dementia is largely unknown. This study aims at evaluating the role of environmental factors on the risk of Alzheimer’s dementia with early onset and other neurodegenerative diseases in a population of Modena in Emilia-Romagna region, Italy. Methods: Using a case-control design, we identified newly-diagnosed EOD cases in the period 2016-2019 in Modena province, while referent population were recruited from caregivers of subjects with dementia. We investigated factors related to environmental exposure, occupational activities, and dietary habits through two tailored questionnaires. The first one collected information about personal characteristics, clinical and family history of diseases and comorbidities, occupational history, hobbies and other leisure activities, residential history, and domestic use of pesticides. We also assessed EOD risk for exposure to light-at-night (LAN) using satellite data into a geographical information system. Finally, we assessed dietary habits by administrating a validated semi-quantitative food frequency questionnaire specifically developed for Northern Italian population evaluating adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. Results: We eventually recruited 58 EOD cases (32 with Alzheimer’s dementia and 19 with fronto-temporal dementia) and 54 controls. 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. About LAN exposure, we found an increase in risk at intermediate exposure categories, though further higher levels of LAN did not show similar OR increase. Finally concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Mediterranean and DASH diets emerged only at very high adherence levels. Conclusions: Our study evaluated possible environmental and occupational risk factors for EOD in Modena population. About clinical history, previous head trauma, atrial fibrillation, stroke, diabetes or dyslipidemia have been positively associated EOD risk. Regarding occupational factors, our findings suggest that use of pesticides, dyes/paints, and metalloids such as aluminum and selenium could be associated with increased disease risk, while no clear association emerged for environmental or residential risk factors including LAN exposure, with the exception of a higher risk associated with smoking. Finally, the association between dietary factors and EOD suggests that adherence to the MIND dietary pattern may linearly decrease such risk. Despite study limitations due to case-control design, including possible occurrence of selection and recall bias but likely to a limited extent, our findings highlighted a possible role of some environmental and lifestyle risk factors in the etiology of young-onset dementia.
Investigation into the environmental risk factors of Alzheimer’s dementia with early onset and other neurodegenerative diseases: An Italian case-control study
27-mag-2022
VINCETI, Marco
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