A summary of the article on “Modifiable risk factors for stroke, dementia and late-life depression: a systematic review and DALY-weighted risk factors for a composite outcome”
Background
The article by Senff J, Tack RWP, Mallick A, et al (2025) published in Journal of Neurology, Neurosurgery & Psychiatry addresses the significant burden of age-related brain diseases, specifically stroke, dementia, and late-life depression (LLD), which are leading causes of disability-adjusted life years (DALYs) globally. It highlights that a substantial portion of these diseases is attributable to modifiable risk factors – at least 60% for stroke, 40% for dementia, and 35% for LLD. A key point is the significant overlap in these modifiable risk factors, largely due to shared underlying pathophysiology, including vascular disease and cerebral small vessel disease (CSVD). Despite this overlap, existing tools often focus on individual diseases or cardiovascular disease combined with stroke, lacking a holistic approach. There is a need to understand the differential impact of overlapping risk factors on the combined burden of these conditions.
Methods
The study’s aim was to systematically identify these overlapping modifiable risk factors and calculate their relative impact on a composite outcome of stroke, dementia, and LLD.
To achieve this, the researchers conducted a systematic literature review of meta-analyses published between January 2000 and September 2023, covering PubMed, Embase, and PsycInfo. They included meta-analyses reporting effect sizes of modifiable risk factors on the incidence of stroke, dementia, and/or LLD. From 182 meta-analyses meeting inclusion criteria, 59 were selected for analysis. They identified 18 modifiable factors that overlapped in at least two of the diseases. For the selected meta-analyses, they calculated disability-adjusted life year (DALY) weighted beta (β)-coefficients for a composite outcome, standardising effect sizes and weighting them according to the disease burden (DALYs) attributed to stroke, dementia, and major depressive disorder. These β-coefficients were then normalised to assess the relative impact of each factor on the composite risk.
Results
The analysis identified 17 modifiable risk factors for which DALY-weighted β-coefficients could be calculated. The normalised β-coefficients provide a measure of the relative impact, where higher positive values indicate a greater risk, and higher negative values indicate a greater protective effect.
Based on the normalised β-coefficients, the factors with the highest risk impact on the composite outcome were:
- Hypertension (normalised β: 130).
- Severe kidney function impairment (normalised β: 101).
- High fasting plasma glucose (normalised β: 94).
- Smoking (normalised β: 91).
Factors demonstrating a significant protective effect included:
- Leisure time cognitive activity (normalised β: −91).
- High levels of physical activity (normalised β: −56).
- Having a purpose in life (normalised β: −50).
Other factors identified with notable impacts (positive βs indicating risk) included BMI (70), sleep duration (76), hearing loss (60), depressive symptoms (57), stress (55), social engagement (53), diet (51), pain (42), and total cholesterol (22). Low alcohol intake (<15 g/day) also showed a protective effect (normalised β: -34), while high intake (>30 g/day) was a risk factor (normalised β: 34).
Conclusions
The findings of this study are crucial as they quantify the relative impact of these shared modifiable risk factors on age-related brain diseases. This provides an empirical foundation for guiding preventative strategies and supports the future development of holistic tools designed to empower individuals to reduce their risk for stroke, dementia, and LLD simultaneously.
Limitations include focusing only on overlapping factors, potential biases like reverse causality (especially for dementia), generalisability issues across diverse populations, and limited published meta-analyses on LLD risk factors.
References
Senff, J., Tack, R. W. P., Mallick, A., Gutierrez-Martinez, L., Duskin, J., Kimball, T. N., Tan, B. Y. Q., Chemali, Z. N., Newhouse, A., Kourkoulis, C., Rivier, C., Falcone, G. J., Sheth, K. N., Lazar, R. M., Ibrahim, S., Pikula, A., Tanzi, R. E., Fricchione, G. L., Brouwers, H. B., … Singh, S. D. (2025). Modifiable risk factors for stroke, dementia and late-life depression: A systematic review and DALY-weighted risk factors for a composite outcome. Journal of Neurology, Neurosurgery & Psychiatry, 96(6), 515–527. https://doi.org/10.1136/jnnp-2024-334925
This post is based on Open Access research and is for informational purposes only.
