Genetic risk for neuroticism increases the risk of Alzheimer’s disease

Could your personality influence your risk of developing Alzheimer’s disease? An analysis of UK Biobank data showed that individuals with amnestic mild cognitive impairment who also have high genetic risk for neuroticism are more likely to develop Alzheimer’s disease. Researchers used genetic data to calculate a neuroticism risk score and found that individuals with higher scores were more prone to developing Alzheimer’s. The paper was published in Human Brain Mapping.

Amnestic mild cognitive impairment is a condition characterized by noticeable memory problems that are more severe than typical age-related changes but not severe enough to interfere significantly with daily life. Individuals with this disorder have difficulty remembering recent events, conversations, or appointments, while other cognitive functions remain largely intact.

Amnestic mild cognitive impairment is considered a transitional stage between normal cognitive aging and Alzheimer’s disease. People with this impairment are at a higher risk of developing Alzheimer’s disease or other dementias, but not all will develop Alzheimer’s or dementia.

Alzheimer’s disease, on the other hand is a progressive neurodegenerative disorder characterized by the buildup of specific proteins in the brain, leading to the death of brain cells and the subsequent decline in cognitive abilities. As the disease advances, individuals become increasingly dependent on others for daily care, ultimately leading to severe impairment and loss of independence.

It remains insufficiently clear why amnestic mild cognitive impairment develops into Alzheimer’s disease in some individuals but not in others. Among various factors, researchers have suggested that neuroticism, a personality trait, can help predict Alzheimer’s development. Genetic studies indicate that neuroticism is 41% to 48% heritable, highlighting its strong genetic basis.

Study author Qiaojun Li and his colleagues wanted to explore whether the genetic risk of neuroticism a person has can be used to predict whether amnestic mild cognitive impairment will develop into Alzheimer’s disease or not. They calculated the neuroticism polygenic risk scores for individuals with amnestic mild cognitive impairment and observed how many of those with low and how many of those with high values of this score will develop Alzheimer’s.

A neuroticism polygenic risk score estimates an individual’s genetic predisposition to neuroticism based on the cumulative effect of multiple genetic variants associated with this personality trait. Neuroticism is characterized by a tendency to experience negative emotions such as anxiety, depression, and irritability, and a greater susceptibility to stress.

The researchers first used data from two genome-wide association studies to develop two neuroticism polygenic risk scores. The first score was based on the results of a UK Biobank study involving 372,903 individuals. The second score was based on data from the Genetics of Personality Consortium involving 73,447 participants.

The researchers applied these scores to data from individuals with amnestic mild cognitive impairment in both the Alzheimer’s Disease Neuroimaging Initiative and the UK Biobank. Using data from 278 individuals from the Alzheimer’s Disease Neuroimaging Initiative and 933 from the UK Biobank, they tested how well their neuroticism polygenic risk scores predicted the development of Alzheimer’s one year and ten years after the study began.

Results from the Alzheimer’s Disease Neuroimaging Initiative showed that neuroticism polygenic risk scores were higher among individuals who developed Alzheimer’s disease after one year, but not after ten years. When participants were divided into high- and low-risk groups, one year after the start of the study, 21% of people in the high-risk group developed Alzheimer’s compared to 11% in the low-risk group. However, after ten years, the differences between the two groups in terms of the proportion of those with Alzheimer’s became too small to be differentiated from random variations.

Similarly, in the UK Biobank data, individuals with amnestic mild cognitive impairment who developed Alzheimer’s also had higher neuroticism polygenic risk scores compared to those who did not develop the condition.

The study sheds light on the links between genes responsible for neuroticism and the development of Alzheimer’s. However, it should be noted that the neuroticism polygenic risk score is not the same as the personality trait of neuroticism and was generally useful only in predicting the development of Alzheimer’s at an earlier stage, but not ten years later.

Further research is needed to refine these predictive tools and to explore the gene-environment interactions that may influence the progression of amnestic mild cognitive impairment to Alzheimer’s. Understanding these mechanisms could lead to more targeted interventions and better outcomes for those at risk of Alzheimer’s disease.

The paper, “Neuroticism polygenic risk predicts conversion from mild cognitive impairment to Alzheimer’s disease by impairing inferior parietal surface area,” was authored by Qiaojun Li, Xingping Lv, Qian Qian, Kun Liao, and Xin Du.