Demographically unadjusted cognitive test scores may enhance the validity of mild cognitive impairment as a dementia prodrome

Mild cognitive impairment (MCI) precedes most forms of neurodegenerative dementias and is considered an important time window for treatment initiation. It is however unclear whether the widespread use of demographically adjusted norms improve detection of dementia-related impairment and identification of individuals at risk for dementia. In the current multicenter study (n = 561), we compared three Petersen/Winblad criteria-based MCI diagnoses with varying levels of demographic adjustments, in relation to their associations with biomarkers for Alzheimer’s disease and neurodegeneration, as well as risk of conversion to future dementia. Our MCI diagnoses were (1) demographically unadjusted; (2) adjusted for sex and education; or (3) adjusted for age, sex, and education. In our cohort, we found the differences between the models to be small, albeit consistent, and our results show a tendency for an unadjusted MCI diagnosis to be more strongly associated to dementia biomarkers and conversion to dementia. Our results thus suggest that an MCI diagnosis based on unadjusted test scores may provide a more valid diagnosis of prodromal dementia, while no evidence is provided to support this in other contexts. This goes against the recommendations from the major diagnostic classification systems, indicating the need for further research to explore these relationships.

轻度认知障碍（Mild Cognitive Impairment, MCI）是多数神经退行性痴呆的前驱阶段，被视为启动治疗的关键时间窗。然而目前尚不清楚，广泛应用人口统计学校正常模是否能提升痴呆相关认知损害的检出效能，以及对痴呆高风险个体的识别准确率。本项多中心研究（样本量n=561）基于彼得森/温布拉德（Petersen/Winblad）诊断标准，设置了三种不同人口统计学校正程度的轻度认知障碍诊断方案，对比其与阿尔茨海默病（Alzheimer’s Disease, AD）及神经退行性变生物标志物的关联，以及向后续痴呆进展的风险。本研究的轻度认知障碍诊断方案分为三类：(1) 未进行人口统计学校正；(2) 校正性别与教育程度因素；(3) 校正年龄、性别与教育程度因素。在本研究队列中，我们发现三类诊断模型间的差异虽较小但具有一致性，且结果显示未校正的轻度认知障碍诊断与痴呆生物标志物、痴呆进展风险的关联强度更高。据此，本研究结果提示，基于未校正测试得分的轻度认知障碍诊断，或许能为前驱性痴呆提供更具效度的诊断依据，但该结论暂未在其他研究场景中得到验证。该结果与主流诊断分类系统的推荐建议相悖，提示需开展进一步研究以明确此类关联。