What are the risk factors for dementia?

Risk Factors for Dementia

Dementia risk is driven by both non-modifiable factors (age, genetics) and a substantial burden of modifiable risk factors, with evidence suggesting that approximately 20-60% of dementia cases could be prevented or delayed through addressing modifiable risk factors across the life course. 1, 2

Non-Modifiable Risk Factors

• Age is the strongest and best-studied risk factor for dementia 3
• Genetics, including first-degree relative with Alzheimer's disease, apolipoprotein ε4 (APOE ε4) genotype, and Down syndrome significantly increase dementia risk 3, 4
• Race and ethnicity influence risk, with highest incidence in Black, Hispanic/Latino Caribbean, and Native American populations; intermediate in Latinx, Mexican American, and non-Latino White populations; and lowest in Japanese American and Asian American populations 1

Modifiable Risk Factors by Life Stage

Midlife Risk Factors (Ages 45-65 Years)

• Hypertension is the primary risk factor for small-vessel ischemic disease and cortical white matter abnormalities underlying both vascular dementia and Alzheimer's disease, with pooled PAF of 15.8% unweighted and 7.1% weighted 1, 5, 6
• Obesity (BMI ≥30 kg/m²) in midlife increases dementia risk, with pooled PAF of 9.4% unweighted and 5.3% weighted 1, 6
• Hearing loss is a significant midlife risk factor with pooled PAF of 15.6% unweighted and 7.2% weighted 1, 6

Late-Life Risk Factors (Ages >65 Years)

• Smoking increases dementia risk, though stopping smoking reduces risk even in later life, with evidence showing benefit from cessation 1, 2
• Depression is a significant risk factor for cognitive decline with substantial impact on dementia incidence 1, 2
• Physical inactivity has pooled PAF of 15.2% unweighted and 7.3% weighted 1, 6
• Social isolation independently increases dementia risk 1, 2
• Diabetes independently increases dementia risk (SHR = 1.56,95% CI 1.00-2.39) 1, 4

Risk Factors Across the Life Course

• Low education has the highest pooled PAF at 17.2% unweighted and 9.3% weighted, making it the single most impactful modifiable risk factor 1, 6
• Cardiovascular disease, including heart disease (SHR = 1.56,95% CI 1.03-2.36) and stroke (SHR = 2.31,95% CI 1.35-3.95), independently increases dementia risk 3, 4
• Hypercholesterolemia (untreated total cholesterol ≥200 mg/dL) contributes to dementia risk 1, 2
• Hyperglycemia (fasting blood glucose ≥100 mg/dL) increases risk 1, 2

Additional Modifiable Risk Factors

• Excessive alcohol consumption increases risk, though light-to-moderate consumption may be protective 1, 2
• Head injury and traumatic brain injury increase dementia risk 1, 2
• Delirium dramatically increases dementia risk (SHR = 8.70,95% CI 3.26-23.24) 4
• Obstructive sleep apnea requires screening and treatment as a modifiable risk factor 1, 2
• Air pollution exposure and second-hand tobacco smoke contribute to dementia risk 2

Combined Risk Factor Impact

• When combining seven key modifiable risk factors (low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes), the pooled unweighted PAF is 55.0% and weighted PAF is 32.0% 6
• Adhering to 4 or all 5 healthy behaviors (weekly moderate/vigorous exercise, not smoking, light-to-moderate alcohol consumption, brain-healthy diet, and cognitive engagement) demonstrates risk reduction of up to 60% 2

Important Considerations

• Frailty modifies dementia risk: individuals with high burden of Alzheimer's disease pathology but low frailty scores are at less risk of meeting criteria for dementia 1
• Timing matters: evidence is stronger for blood pressure lowering in middle age (45-64 years) than in older adults for preventing dementia 5
• Geographic disparities: pooled PAF values for most individual risk factors are higher in low-income and middle-income countries versus high-income countries 6
• Health equity concerns: chronic stress, smoking, pollution exposure, and inequitable access to education, healthy diet, and health care disproportionately affect underrepresented populations and contribute to higher dementia incidence 1

Clinical Pitfall

The LIBRA index demonstrates that modifiable risk factors predict dementia in midlife (55-69 years) and late life (70-79 years), but not in the oldest-old (80-97 years), suggesting that prevention interventions should target individuals before age 80 7