New breakthrough in Alzheimer's disease research! Mild cognitive impairment hides risk "code"

As the global population ages, cognitive impairment diseases such as Alzheimer's disease are increasingly becoming a major challenge in the field of public health. In the development of these diseases, neuropsychiatric symptoms such as apathy, depression, and aggression not only seriously affect the quality of life of patients, but are also considered to be important markers of disease progression. However, previous studies have mostly focused on the analysis of single neuropsychiatric symptoms, lacking in-depth discussions on the interactions between neuropsychiatric symptoms and their long-term relationship with cognitive changes. Recently, a research team from Columbia University published a study in the journal Biological Psychiatry, aiming to systematically analyze the classification characteristics of neuropsychiatric symptoms in patients with mild cognitive impairment and early Alzheimer's disease, as well as the long-term relationship between these symptoms and cognitive changes, in order to find new ways to identify and manage the risk of Alzheimer's disease early.

Research Process

The data for this study came from the famous Alzheimer's Disease Neuroimaging Initiative, a database that contains a large amount of detailed clinical and imaging data on patients with Alzheimer's disease and mild cognitive impairment. The research team carefully selected 1,472 patients who were diagnosed with mild cognitive impairment or Alzheimer's disease at baseline and had neuropsychiatric symptom scores as research subjects.

In order to comprehensively evaluate the neuropsychiatric symptoms of these patients, the study used the Neuropsychiatric Rating Scale or its simplified version. These scales record in detail the frequency and severity of neuropsychiatric symptoms such as delusions, hallucinations, agitation, depression, anxiety, etc. that occur in patients within a month to obtain the Neuropsychiatric Rating Scale score. The higher the score, the more severe the neuropsychiatric symptoms. In addition, the study also used a functional assessment questionnaire to evaluate the patient's daily functional performance, as well as a variety of other clinical tests such as the Mini-Mental State Examination, the Clinical Dementia Rating Scale, and the Geriatric Depression Scale to fully understand the patient's cognitive and functional status.

During the data analysis phase, the research team used advanced statistical models to classify the patients' neuropsychiatric symptoms and analyzed the long-term relationship between different neuropsychiatric symptom categories and cognitive changes. They paid special attention to the association between neuropsychiatric symptom categories and the risk of transition from mild cognitive impairment to Alzheimer's disease.

Research Findings

After in-depth analysis, the research team identified three main neuropsychiatric symptom categories: no neuropsychiatric symptoms, apathy/emotionality, and complex neuropsychiatric symptoms. Among them, the no neuropsychiatric symptom group accounted for 51.7% of the sample, and these patients showed almost no neuropsychiatric symptoms; the apathy/emotionality group accounted for 39.8%, mainly manifested as apathy, depression, irritability and anxiety; and the complex neuropsychiatric symptom group accounted for 8.5%, and these patients had multiple neuropsychiatric symptoms at the same time, and the symptoms were more severe.

The study found that compared with the group without neuropsychiatric symptoms, the complex neuropsychiatric symptom group and the apathy/emotional group performed worse on all cognitive tests at baseline. In particular, the complex neuropsychiatric symptom group performed significantly worse than the other two groups in tests such as immediate memory and clock drawing. Over time, the daily functional performance of these groups also declined significantly faster than that of the group without neuropsychiatric symptoms.

More importantly, the study revealed a significant association between the category of neuropsychiatric symptoms and the risk of transformation from mild cognitive impairment to Alzheimer's disease. After adjusting for covariates, complex neuropsychiatric symptoms were associated with a 103% increased risk of progression to Alzheimer's disease in patients with mild cognitive impairment, while apathy/emotionality was associated with a 39% increased risk of progression to Alzheimer's disease. Simply put, if patients with mild cognitive impairment develop complex neuropsychiatric symptoms or apathy/emotionality, their likelihood of developing AD in the future will be greatly increased. Therefore, these symptoms can serve as early warning signs for identifying AD risk.

Future Outlook

The results of this study provide a new perspective for early identification and management of Alzheimer's disease risk. By identifying specific neuropsychiatric symptom categories, doctors can more accurately predict the risk of mild cognitive impairment patients developing Alzheimer's disease, thereby achieving early intervention. At the same time, the development of specific intervention strategies for different neuropsychiatric symptom categories is expected to become a new way to delay the progression of Alzheimer's disease and improve the quality of life of patients.

In the future, the research team will further expand the sample size and explore the biological mechanisms of neuropsychiatric symptoms and cognitive changes. At the same time, combining genetic, imaging and other multi-dimensional data to build a more comprehensive Alzheimer's disease risk assessment model is also a research direction worth looking forward to.

Reference: Park JI, Lee S, Huber B, et al. Empirical classification of neuropsychiatric symptoms and association of classes with diagnostic progression and cognitive decline in MCI and AD populations. Biol Psychiatry. Published online February 6, 2025. doi:10.1016/j.biopsych.2025.01.026