# Assessment of Risk Factors for Cognitive Impairment Accounting for Genetic and Environmental Influences: An Italian Population-Based Twin Study

## TL;DR

This study uses Italian twins to explore how genetic and environmental factors influence the link between risk factors and cognitive impairment.

## Contribution

The study introduces matched-pair analyses in twins to infer quasi-causality and detect genetic or environmental confounding.

## Key findings

- Hearing loss's link to cognitive impairment weakened in matched-pair analyses, suggesting genetic or environmental confounding.
- Sleep disturbances showed strong and consistent associations with cognitive impairment, indicating a genuine effect.
- The study highlights the need for longitudinal research to confirm quasi-causal relationships in cognitive decline.

## Abstract

Background/Objectives: The etiology of dementia is complex and multifactorial, with both genetic and environmental factors contributing to its onset. The Lancet Commission has identified several risk factors for this condition, but it is increasingly urgent to confirm their etiological role while accounting for both measured and unmeasured confounding effects. Our study, conducted on a population-based sample of Italian twins, examines the link between known risk factors and cognitive impairment, and the contribution of genetic and environmental influences to this link. Methods: Study participants were adult twins from the Italian Twin Registry who completed self-administered questionnaires. Cognitive impairment was evaluated by the SAGE questionnaire, while risk factors were assessed using the checklist proposed by the Lancet Commission. Individual-level and matched-pair analyses were performed for each risk factor, and their results were compared to detect potential genetic or environmental confounding, and to infer “quasi-causality” in the examined associations. Results: A total of 483 twins participated in the study (mean age 69.14 years, 63% women, 47% monozygotic twins). In matched-pair analyses, the association between hearing loss and cognitive impairment decreased in magnitude and became non-significant, suggesting confounding by genetics or early-life environment; in contrast, the association with sleep disturbances resulted strong and significant in both individual-level and matched-pair analyses, indicating a genuine effect of sleep on cognition. Conclusions: Our findings suggest a potential “quasi-causal” role of sleep disorders in cognitive decline. This relationship should be clarified through well-powered longitudinal studies incorporating precise clinical definitions and biomarker data.