Study finds gene variant tied to faster cognitive decline in Taiwanese

Taipei, March 17 (CNA) A research team at Taiwan's National Health Research Institutes (NHRI) has found that middle-aged and older Taiwanese carrying the APOE4 gene variant experienced faster cognitive decline over time, the first such finding for a Taiwanese population.

The APOE4 gene variant, one of four APOE variants, has been associated with Alzheimer's disease since the early 1990s, according to a Stanford Medicine report in September 2025, and several studies have looked at APOE4's prevalence in different populations.

But the NHRI study was the first to confirm that the APOE4 gene was associated with accelerated cognitive decline in a population of cognitively healthy middle-aged and older Taiwanese, NHRI researcher Chung Yu-chu (鍾宇筑) said at a press conference Monday.

"These results highlight the potential utility of early genetic risk awareness and support consideration of targeted preventive strategies for APOE4 carriers," the NHRI team wrote in the study, published in JAMA Network Open on March 6.

Though APOE4 carrier status has been associated with an increased risk of Alzheimer's disease, the mechanism is not yet clear.

NHRI researcher Lai Rai-hua (賴瑞華) said the APOE gene plays a role in regulating blood lipid levels and metabolizing and clearing harmful proteins, while the fourth variant may also be associated with severe chronic inflammation and stress hormones.

The APOE4 gene variant may therefore contribute to the buildup of amyloid, an abnormal, insoluble protein that can accumulate in the brain, and is considered the most common genetic risk factor for late-onset Alzheimer's disease, he said.

Study details

To find out whether APOE4 is associated with faster cognitive decline in Taiwan, the team analyzed data from 4,392 adults aged 55 and older who had not been diagnosed with dementia.

Of those participants, 33 carried two copies of APOE4, 723 carried one copy, and the rest were non-carriers, according to the study.

Using results from the Mini-Mental State Examination (MMSE), a commonly used test of cognitive function, researchers tracked changes in participants' cognition across at least two time points over an average period of about six years.

The team found that middle-aged and older adults carrying one or two copies of APOE4 experienced significantly faster cognitive decline than non-carriers, with the gap widening after age 70.

Those carrying two copies of APOE4 showed the fastest decline, the team said, suggesting a dose-dependent pattern in which "the more copies a person carries, the more pronounced the acceleration in cognitive decline."

The study found that 17.3 percent of Taiwanese carry at least one copy of the gene variant, lower than the 20-30 percent of carriers in white populations, Lai said, based on previous studies.

Lai said no therapy targeting the APOE4 gene variant has entered the clinical trial stage, but he hoped the study could inform an early detection program.

He also suggested that people who know they have the APOE4 variant should focus on lifestyle habits, such as eating more vegetables and fiber-rich foods, consuming less fat, and exercising more, to reduce the risk of cognitive decline.

According to a 2023 survey conducted by the NHRI and the Ministry of Health and Welfare, the prevalence of dementia among people aged 65 and older in Taiwan was close to 8 percent, meaning about one in every 13 older adults had the condition.