What are the 12 risk factors for dementia

Lon Schneider, MD

An update to the Lancet Commission report on dementia prevention, intervention, and care published by 28 world-leading dementia experts and presented at the 2020 Alzheimer's Association International Conference (AAIC) annual meeting, July 26—30, outlines 12 potentially modifiable risk factors to prevent or delay up to 40% of cases of dementia.1

Presented at AAIC 2020 by Lon Schneider, MD, co-director of the University of Southern California Alzheimer Disease Research Center, and professor of psychiatry and neurology at Keck School of Medicine, the authors found that 9 potentially modifiable risk factors for people in low income and middle income (LMIC) countries together are associated with 35% of the population attributable fraction (PaFs) of dementia worldwide. Among them are less education, high blood pressure, obesity, hearing loss, depression, diabetes, physical inactivity, smoking, and social isolation, assuming causation.

In this report, Schneider and colleagues identified and explained which risk factors may lead to increased dementia incidence by using data from previous studies and meta-analyses. The current report, which is an update to the 2017 Lancet Commission, also now includes 3 new risk factors: excessive alcohol intake, head injury, and air pollution. “We are learning that tactics to avoid dementia begin early and continue throughout life, so it’s never too early or too late to take action,” Schneider said in a statement.2

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Mid-life hearing loss

Hearing loss had the highest PaF for dementia in the report, which was based off a meta-analysis of studies of people with normal baseline cognition and hearing loss present with a threshold of 25 db. Researchers found a risk ratio (RR) of 1.9 for dementia in populations followed up over 9 to 17 years in the 2017 Lancet Commission report.

Education

Higher childhood education levels and lifelong higher educational attainment is associated with increased overall cognitive ability and reduced dementia risk. Previous studies had shown that the brain reaches greatest plasticity in late adolescence, with relatively few further gains with education after age 20. Schneider and colleagues noted, “It is difficult to separate out the specific impact of education from the effect of overall cognitive ability, and the specific impact of later-life cognitive activity from lifelong cognitive function and activity.”

Traumatic brain injury (TBI)

Findings from a Danish cohort study showed an increased risk for dementia (HR, 1.2; 95% CI, 1.2—1.3) and Alzheimer disease (AD) (HR, 1.2; 95% CI, 1.1–1.2) in those who experienced TBI. Dementia risk was highest in the 6 months after TBI (HR, 4.1; 95% CI; 3.8–4.3) and increased with number of injuries in people with TBI (1 TBI, HR, 1.2; 95% CI, 1.2–1.3; ≥5 TBIs, HR, 2.8; 95% CI, 2.1–3.8).

Hypertension

In the Framingham Offspring cohort comprising 1440 people, elevated systolic blood pressure (≥140 mm Hg in midlife; mean age 55 years) was associated with an increased risk of developing dementia (HR, 1.6; 95% CI, 1.1—2.4) over an 18-year follow-up period. Hypertension that persisted into later life was associated with an increased risk of dementia, as well (mean age, 69; HR, 2.0; 95% CI, 1.3–3.1).

Physical inactivity

Schneider and colleagues referred to the HUNT study, which showed that weekly midlife moderate —to vigorous physical activity was associated with reduced dementia risk over a 25-year period of follow up (HR, 0.8; 95% CI; 0.6–1.1). They also concluded, “People might stop exercising due to prodromal dementia so inactivity might be either a consequence or a cause or both in dementia and might be more of a risk in those with cardiovascular morbidity. As with other outcomes, exercise might be required to be sustained and continue nearer the time of risk.”

Diabetes

The 2017 Lancet Commission report included 2.3 million individuals with type 2 diabetes, as well as 102,174 with dementia; diabetes was associated with an increased risk of dementia (RR, 1.6; 95% CI; 1.5—1.8 for women and RR, 1.6; 95% CI, 1.4–1.8 for men). Additionally, the risk of dementia increased with the duration and severity of diabetes.

Excessive alcohol consumption

Heavy drinking is associated with brain changes, cognitive impairment, and dementia, which was further confirmed in a French 5-year longitudinal study of over 31 million people. In that study, alcohol use disorders were associated with increased dementia risk, calculated separately for men and women (women: HR, 3.3; 95% CI, 3.3—3.4; men: HR, 3.4; 3.3–3.4). Among those with earlier onset dementia, 56.6% had an alcohol use disorder noted in their health history.

Weight control and obesity

A review of 19 longitudinal studies showed that obesity (Body mass index (BMI) ≥30; RR, 1.3; 95% CI, 1.1—1.6) but not being overweight (BMI 25–30; RR, 1.1; 95% CI, 1.0–1.2) was associated with late-life dementia. Additionally, higher body mass measured before probable preclinical and prodromal dementia was associated with increased dementia risk (RR, 1.3; 95% CI, 1.1–1.7).

Smoking

Smokers are at a greater risk of dementia, but stopping smoking, even when older, can reduce that risk. A cohort of 50,000 men older than 60 years who stopped smoking for more than 4 years, compared with continuing, substantially reduced dementia risk over the subsequent 8 years (HR, 0.9; 95% CI, 0.7—1.0). Another study indicated that second-hand smoke exposure, found in 35% of nonsmoking adults, was associated with more memory deterioration.

Depression

A meta-analysis of 32 studies revealed that a depressive episode was indeed a risk factor for dementia (pooled effect size = 2.0; 95% CI, 1.7—2.3). Additionally, there was a non-significant trend for the association between depression and incident dementia to be weaker when the length of follow-up was longer. Schneider and colleagues pointed to a multitude of studies, including the UK Whitehall study and the Norwegian HUNT study, that explain the association between depression and increased dementia incidence.

Social contact

Social contact is an accepted protective factor that enhances cognitive reserve or encourages beneficial behaviors. Less social contact has been proven to increase the risk of dementia, as observed in multiple studies. Study authors referred to a Japanese longitudinal cohort study that calculated a 5-point social contact scale, with those who scored highest having a 46% less likely chance to develop incident dementia compared with those in the lowest category.

Air pollutants

Animal models have suggested that airborne particulate pollutants accelerate neurodegenerative processes through cerebrovascular and cardiovascular disease, amyloid-beta deposition, and amyloid precursor protein processing. Although the higher levels of dementia from air pollutants are still subject to the potential for residual confounding, the effects on animal models are evidence of physiological effects over and above those driven by life-course deprivation.

“Knowledge about risk factors and potential prevention, detection, and diagnosis of dementia is improving although significant gaps remain. In this Commission report, we have specified policy and individual changes to delay the onset of cognitive impairment and dementia and better ways to support and treat people with dementia and their families and to improve their quality of life,” Schneider and colleagues concluded.

REFERENCES

1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. Published online July 30, 2020. doi: 10.1016/S0140-6736(20)30367-6

2. An update to the Lancet Commission on dementia prevention, intervention and care adds excessive alcohol intake, head injury and air pollution to nine previously identified modifiable risks [news release]. Los Angeles, CA. Published July 30, 2020. Accessed August 3, 2020.

Researchers have identified several risk factors that affect the likelihood of developing one or more kinds of dementia. Some of these factors are modifiable, while others are not.

Age. The risk of Alzheimer's disease, vascular dementia, and several other dementias goes up significantly with advancing age.

Genetics/family history. Researchers have discovered a number of genes that increase the risk of developing Alzheimer's disease. Although people with a family history of Alzheimer's disease are generally considered to be at a heightened risk of developing the disease themselves, many people who have relatives with Alzheimer's disease never develop the disease, and many without a family history of the disease do get it.

In most cases, it is impossible to predict a specific person's risk of the disorder based on family history alone. Some families with Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, or fatal familial insomnia have mutations in the prion protein gene, although these disorders can also occur in people without the gene mutation. Individuals with these mutations are at significantly higher risk of developing these forms of dementia.

Abnormal genes are also clearly implicated as risk factors in Huntington's disease, FTDP-17, and several other kinds of dementia.

Many people with Down's syndrome show neurological and behavioral signs of Alzheimer's disease by the time they reach middle age.

Smoking and alcohol use. Several recent studies have found that smoking significantly increases the risk of mental decline and dementia. People who smoke have a higher risk of atherosclerosis and other types of vascular disease, which may be the underlying causes for the increased dementia risk.

Studies also have found that drinking large amounts of alcohol appears to increase the risk of dementia. However, other studies have suggested that people who drink moderately have a lower risk of dementia than either those who drink heavily or those who completely abstain from drinking.

Atherosclerosis. Atherosclerosis is the buildup of plaque – deposits of fatty substances, cholesterol, and other matter – in the inner lining of an artery.

Atherosclerosis is a significant risk factor for vascular dementia, because it interferes with the delivery of blood to the brain and can lead to stroke. Studies have also found a possible link between atherosclerosis and Alzheimer's disease.

Cholesterol. High levels of low-density lipoprotein (LDL), the so-called "bad" form of cholesterol, appear to significantly increase a person's risk of developing vascular dementia. Some research has also linked high cholesterol to an increased risk of Alzheimer's disease.

Plasma homocysteine. Research has shown that a higher-than-average blood level of homocysteine, a type of amino acid, is a strong risk factor for the development of Alzheimer's disease and vascular dementia.

Diabetes. Diabetes is a risk factor for both Alzheimer's disease and vascular dementia. It is also a known risk factor for atherosclerosis and stroke, both of which contribute to vascular dementia.

Mild cognitive impairment. While not all people with mild cognitive impairment develop dementia, people with this condition do have a significantly increased risk of dementia compared to the rest of the population. One study found that approximately 40 percent of people over age 65 who were diagnosed with mild cognitive impairment developed dementia within three years.