Age, Gender, and APOE4 Variant May Help Identify Those at High Risk for Dementia, Study Suggests

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by Alice Melão |

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The absolute 10-year risk of dementia varies according to age, gender, and common variation in the APOE gene, according to a large-scale Danish study.

This discovery may help identify high-risk individuals who may benefit from early targeted intervention to prevent dementia’s development and progression.

The study, “Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study,” was published in the Canadian Medical Association Journal.

“Recently, it was estimated that one-third of dementia most likely can be prevented. According to the Lancet Commission, early intervention for hypertension, smoking, diabetes, obesity, depression, and hearing loss may slow or prevent disease development,” Ruth Frikke-Schmidt, from the Rigshospitalet, Copenhagen University Hospital, and senior author of the study, said in a press release.

“If those individuals at highest risk can be identified, a targeted prevention with risk-factor reduction can be initiated early before disease has developed, thus delaying onset of dementia or preventing it,” she said.

The team reviewed the clinical records of 104,537 individuals who had participated in the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Among these individuals, 2,160 developed dementia and 7,520 cerebrovascular disease.

It is believed that APOE gene variants can directly affect brain tissue, blood-brain barrier, and blood vessels, resulting in alterations to brain functions.  The apoE4 protein, a protein involved in lipid metabolism, is present in about 65-80% of patients with Alzheimer’s. Reports have suggested that the apoE protein is involved in beta-amyloid protein clearance and burden, which is impaired in Alzheimer’s disease.

Analysis of APOE variants revealed that the absolute 10-year risk of having dementia changed, with a higher risk associated with the presence of the APOE4 variant and different age groups.

Women who carried two copies of APOE4 variant ages 60–69, 70–79, and 80 years and up had a 7%, 16% and 24% absolute 10-year risk of Alzheimer’s disease, respectively. Men with this APOE4 variant in the same age groups had a 6%, 12% and 19% increased risk of Alzheimer’s, respectively.

When taking into consideration other types of dementia, including vascular dementia or dementia of unknown cause, the corresponding 10-year risk within the same age ranges were 10%, 22% and 38% for women, and 8%, 19% and 33% for men.

“The present absolute 10-year risk estimates of dementia by age, sex and common variation in the APOE gene have the potential to identify high-risk individuals for early targeted preventive interventions,” researchers said.

Those who had two copies of the APOE4 variant had a risk of developing Alzheimer’s disease 8.74 times higher than those with two copies of the most common variant, APOE3. They also had a 2.87 and 4.68 times higher risk of vascular dementia and unspecified dementia.

Other factors found to independently contribute to the risk of all dementia included smoking (68% increased risk), diabetes mellitus (30%), and physical inactivity (16%). In contrast, high blood pressure and lipid-lowering therapy in men were associated with a decreased risk of developing any dementia.

Also, individuals with APOE4 variant were found to have an increased risk of cardiovascular diseases, including ischemic cerebrovascular disease and hemorrhagic stroke.

“Taken together, the present findings emphasize APOE genotype [genetic variants] as an important component in the individual risk assessment of dementia and cerebrovascular disease,” researchers said.