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Dementia: Risk Factors

Original Editor - lucinda hampton

Top Contributors - Lucinda hampton, Tolulope Adeniji and Kim Jackson  

Introduction

Dementia risk factors are divided into two categories: modifiable and non-modifiable. Modifiable risk factors include lifestyle choices such as physical inactivity, tobacco use, unhealthy diets, and excessive alcohol consumption. Medical conditions like hypertension, diabetes, high cholesterol, obesity, and depression also increase dementia risk. Social isolation and cognitive inactivity are additional modifiable factors that may contribute to dementia risk.

Non-modifiable risk factors primarily consist of age and genetics. Age is the most significant risk factor for dementia, though it's important to note that dementia is not an inevitable consequence of aging. Genetic predisposition can also play a role in increasing dementia risk.

Recent research provides more detailed insights into dementia risk:

  1. The lifetime risk of developing dementia after age 55 is approximately 42%.
  2. Certain groups face higher lifetime risks, ranging from 45% to 60%:
    • Women
    • Black adults
    • Carriers of the APOE ε4 gene variant
  1. In the United States, projections indicate: Annual new dementia cases are expected to rise from about 514,000 in 2020 to around 1 million by 2060. This increase is particularly pronounced among Black adults.
  1. These findings underscore the importance of:
  • Implementing policies that promote healthy aging
  • Addressing health disparities
  • Encouraging patient involvement in dementia prevention strategies

Understanding both modifiable and non-modifiable risk factors is crucial for developing effective prevention and management strategies for dementia. This knowledge can inform public health planning and guide individuals in taking proactive steps to reduce their dementia risk.[1]

Environmental risk factors

19 reviews containing 37 meta-analyses (2025) report:

  • Exposure to 9 environmental risk factors were associated with higher risks of all-cause dementia: fine particulate matter, particulate matter, nitrogen dioxide, nitrogen oxides, carbon monoxide, shift work, night shift work, chronic noise, and extremely-low frequency magnetic fields.
  • Neighbourhood greenness was associated with a lower risk of all-cause dementia.
  • In a narrative review, we found that exposure to sulfur dioxide, proximity to roadways, ionizing radiation, aluminum, solvents, pesticides, and environmental tobacco smoke were also associated with dementia.
  • Fine particulate matter, extremely-low frequency magnetic fields, sulfur dioxide, chronic noise, and pesticides were related to Alzheimer's disease dementia.
  • Fine particulate matter, particulate matter, and chronic noise were related to vascular dementia.

Achieving stronger air quality targets has the potential to reduce population-level dementia risk. Neighbourhood (i.e., greenness and chronic noise) and occupational (i.e., shift work) characteristics are associated with dementia and are viable public health intervention points. Additional research should examine the relationship between other environmental risk factors and mild cognitive impairment and specific types of dementia.[2]

Risk Factors

  1. Diabetes mellitus is a significant risk factor for dementia. It contributes to dementia development through glucose-mediated toxicity, causing microvascular abnormalities and neurodegeneration. Impaired insulin receptor activation in Alzheimer's disease suggests an insulin-resistant brain state. Midlife type 2 diabetes increases the risk of various forms of dementia and cognitive impairment. Longer duration and greater severity of diabetes further increase dementia risk. Studies show diabetes is associated with a 47% increased risk of any dementia, 39% increased risk of Alzheimer's disease, and 138% increased risk of vascular dementia.[3] [4] [5]
  2. Physical inactivity: Physical activity, especially in midlife, reduces dementia risk. Exercise has neuroprotective effects through BDNF release, cortisol reduction, and vascular risk reduction. A meta-analysis found higher levels of physical activity offer greater protection against cognitive decline. A study showed moderate-intensity walking increased hippocampal volume and improved memory in older adults, while stretching and toning did not. This suggests physical activity can promote brain growth and enhance cognitive function in aging..[6][7][8] [9] [10] [11]
  3. Depression: Depression doubles as a risk factor and a symptom of dementia. It is biologically probable that depression increases dementia risk as it affects stress hormones, neuronal growth factors, and hippocampal volume.[12] Cohort studies[13] with extended follow-up times show a link between number of depressive episodes and risk of dementia, which further reinforces the assertion that depression is a risk factor for dementia. However, a cohort study[14] suggests that midlife depression is not a risk factor for dementia.
  4. Smoking: Smoking is believed to be associated with dementia and cognitive decline[15] due to its effect on cardiovascular pathology. A meta-analysis[16] has shown that current smoking increased the risk of dementia (from any cause) by a significant amount (34% for every 20 cigarettes consumed per day). However, former smokers were found to have a similar risk profile to those who had never smoked. This suggests that by giving up smoking, individuals can potentially reduce their dementia risk to that of someone who has never smoked.
  5. Midlife Hypertension: has also been associated with increased risk of dementia in late life[17].
  6. Midlife obesity: is associated with increased risk of cardiovascular disease, vascular dementia, and Alzheimer's disease. A systematic review and meta-analysis of observational studies involving about 600,000 individuals found that obesity in midlife increases dementia risk (RR = 1.33; 95% CI: 1.08-1.63). Notably, being overweight did not show the same increased risk.[18]
  7. Low education: A 2020 systematic review examined the relationship between education and dementia risk. Low education is considered a modifiable risk factor for dementia, but the study found inconsistencies in defining and measuring education across dementia studies. Meta-analysis results showed each year of education reduced risk by 8% for Alzheimer's Disease and 7% for any dementia. Low education increased risk by 45% for any dementia and 85% for Alzheimer's Disease, though definitions of "low education" varied widely from 0 to 12 years. While the association between low education and dementia risk is robust, inconsistent definitions hinder practical policy recommendations.[19]
  8. Hearing loss: it has also been associated with an increased risk for dementia or cognitive decline.[20] A recent meta-analysis of prospective cohort studies showed that the relative risk of hearing impairment on incident Alzheimer’s and MCI was 2.82 (95% CI: 1.47–5.42)[21]. In addition, a meta-analysis published by the Lancet Commission showed that hearing loss can almost double the risk of incident dementia (RR = 1.94, 95% CI: 1.38–2.73)[22]
  9. Sleep disturbances: Sleep disturbances have emerged as a significant modifiable risk factor for dementia. Poor sleep quality, including insomnia, sleep apnea, and fragmented sleep, has been linked to increased amyloid-beta accumulation in the brain, a hallmark of Alzheimer’s disease.[23] Research suggests that individuals with chronic sleep deprivation or irregular sleep patterns are at a higher risk of developing cognitive decline and dementia. Therefore, promoting good sleep hygiene, including regular sleep schedules and addressing sleep disorders, may be an important strategy in reducing dementia risk
  10. Social Isolation: Social disengagement has been shown to increase risk of cognitive impairment and dementia in older individuals[24]. A systematic review and meta-analysis of longitudinal cohort studies showed that lower social participation, less frequent social contact and loneliness were associated with higher rates of incident dementia.[25] Additionally, research indicates that social isolation can lead to increased stress, depression, and cardiovascular issues, which may further contribute to the development of cognitive decline and dementia[26]

ANU Alzheimer's Disease Risk Index

ANU Alzheimer's Disease Risk Index (ANU-ADRI) is an evidence-based, validated, tool aimed at assessing an individual's exposure to risk factors known to be associated with an increased risk of developing Alzheimer's disease in late-life(> 60 years)

References

  1. ↑ Fang M, Hu J, Weiss J, Knopman DS, Albert M, Windham BG, Walker KA, Sharrett AR, Gottesman RF, Lutsey PL, Mosley T. Lifetime risk and projected burden of dementia. Nature Medicine. 2025 Jan 13:1-5.Available:https://pubmed.ncbi.nlm.nih.gov/39806070/ (accessed 21.4.2025)
  2. ↑ Jones A, Ali MU, Mayhew A, Aryal K, Correia RH, Dash D, Manis DR, Rehman A, O’Connell ME, Taler V, Costa AP. Environmental risk factors for all-cause dementia, Alzheimer’s disease dementia, vascular dementia, and mild cognitive impairment: An umbrella review and meta-analysis. Environmental Research. 2025 Jan 29:121007. BibTeXEndNoteRefManRefWorks Available:https://pubmed.ncbi.nlm.nih.gov/39889875/( accessed 21.4.2025)
  3. ↑ Frölich L, Blum-Degen D, Bernstein HG, et al. Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. J Neural Transm (Vienna) 1998; 105: 423–38.
  4. ↑ Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 2006; 5: 64–74
  5. ↑ Lu FP, Lin KP, Kuo HK. Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. 2009,4(1)
  6. ↑ Andel R, Crowe M, Pedersen NL, Fratiglioni L, Johansson B, Gatz M. Physical exercise at midlife and risk of dementia three decades later: a population-based study of Swedish twins. J Gerontol A Biol Sci Med Sci 2008; 63: 62–66.
  7. ↑ Vaughan S, Wallis M, Polit D, Steele M, Shum D, Morris N. The effects of multimodal exercise on cognitive and physical functioning and brain-derived neurotrophic factor in older women: a randomised controlled trial. Age Ageing 2014; 43: 623–29.
  8. ↑ Leckie RL, Oberlin LE, Voss MW, et al. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front Hum Neurosci 2014; 8: 985.
  9. ↑ Young J, Angevaren M, Rusted J, Tabet N. Aerobic exercise to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 2015; 4: CD005381.
  10. ↑ Sofi F, Valecchi D, Bacci D, et al. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med 2011; 269: 107–17
  11. ↑ Kirk I  Erickson, Michelle W. Voss, Ruchika Shaurya Prakash, Chandramallika Basak, e Amanda Szabo et al. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of the USA, 108, 3017-3022
  12. ↑ Alexopoulos GS. Vascular disease, depression, and dementia. J Am Geriatr Soc 2003; 51: 1178–80
  13. ↑ Dotson VM, Beydoun MA, Zonderman AB. Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology 2010; 75: 27–34.
  14. ↑ Singh-Manoux A, Dugravot A, Fournier A, et al. Trajectories of depressive symptoms before diagnosis of dementia a 28-year follow-up study. JAMA Psychiatry 2017
  15. ↑ Durazzo TC, Mattsson N, Weiner MW, Alzheimer's Disease Neuroimaging Initiative. Smoking and increased Alzheimer's disease risk: a review of potential mechanisms. Alzheimer's & Dementia, 2014;10(3):S122–S145.
  16. ↑ Zhong G, Wang Y, Zhang Y, Guo JJ, Zhao Y. Smoking Is Associated with an Increased Risk of Dementia: A Meta-Analysis of Prospective Cohort Studies with Investigation of Potential Effect Modifiers.2015
  17. ↑ Kivipelto M, Mangialasche F, Ngandu T, World Wide Fingers Network. World Wide Fingers will advance dementia prevention. Lancet Neurology. 2017. 17(1):27.
  18. ↑ Albanese E, Launer LJ, Egger M, Prince MJ, Giannakopoulos P, Wolters, FJ et al. Body mass index in midlife and dementia: systematic review and meta-regression analysis of 589,649 men and women followed in longitudinal studies. Alzheimer's & Dementia. 2017 8:165–178.
  19. ↑ Maccora J, Peters R, Anstey KJ. What does (low) education mean in terms of dementia risk? A systematic review and meta-analysis highlighting inconsistency in measuring and operationalising education. SSM-population health. 2020 Dec 1;12:100654.Available: https://pmc.ncbi.nlm.nih.gov/articles/PMC7721642/#abs0010(accessed 21.4.2025)
  20. ↑ Lin FR, Yaffe K, Xia J, Xue QL, Harris TB, Purchase-Helzner E et al. Hearing loss and cognitive decline in older adults. JAMA Internal Medicine.(2013) 173(4):293–299.
  21. ↑ Zheng Y, Fan S, Liao W, Fang W, Xiao S, Liu J . Hearing impairment and risk of Alzheimer’s disease: a meta-analysis of prospective cohort studies. Neurological Sciences.(2017) 38(2):233–239
  22. ↑ Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D et al. (2017). Dementia prevention, intervention, and care. Lancet. 390(10113):2673–2734.
  23. ↑ Wang C, Holtzman DM. Bidirectional relationship between sleep and Alzheimer’s disease: role of amyloid, tau, and other factors. Neuropsychopharmacology. 2020 Jan;45(1):104-20.
  24. ↑ Fratiglioni L, Paillard-Borg S, Winblad B . An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurology.2004: 3(6):343–353.
  25. ↑ Kuiper JS, Zuidersma M, Voshaar RCO, Zuidema SU, van den Heuvel ER, Stolk RP et al. Social relationships and risk of dementia: a systematic review and meta-analysis of longitudinal cohort studies. Ageing Research Reviews. 2015: 22:39–57.
  26. ↑ Cené, C., Beckie, T., Sims, M., Suglia, S., Aggarwal, B., Moise, N., Jimenez, M., Gaye, B., & McCullough, L. (2022). Effects of Objective and Perceived Social Isolation on Cardiovascular and Brain Health: A Scientific Statement From the American Heart Association. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 11. https://doi.org/10.1161/JAHA.122.026493.
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