Predictors of bi-directional transitions from mild cognitive impairment in a diverse cohort

Mitzi M Gonzales, Roman Fernandez, Sarah Kremen, Zaldy S Tan, Amy E Werry, Xueqiu Jian, John Hart, Donald Royall, Gladys Maestre, Sara Espinoza, Sudha Seshadri, Jonathan Gelfond, Chen-Pin Wang
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Abstract

Trajectories following a diagnosis of mild cognitive impairment (MCI) are varied and may fluctuate over time. Among diverse ethnic and racial groups, social factors, medical comorbidities, and biases in assessment procedures may contribute to greater heterogeneity in the MCI diagnostic category and affect its prognostic significance for dementia. The study goal was to evaluate the frequency and variables associated with MCI transitions among non-Hispanic White (NHW) and Latinx older adults. Multistate Markov models characterized transitions across diagnostic states (cognitively unimpaired (CU), MCI, dementia) over ten years. Variables associated with transitions were assessed using hazard ratios (HR) and 95% confidence intervals (CIs). The study included 413 participants (58% female, mean age 72+8, 52% Latinx ethnicity). Following an MCI diagnosis, the likelihood of converting to dementia versus reverting to CU were equally probable. Older age, NHW ethnicity, APOE ε4, diabetes, lower BMI, and higher neuropsychiatric symptoms associated with elevated risk for dementia conversion, whereas younger age and lower neuropsychiatric symptoms associated with CU reversion. Above other factors, higher baseline serum glial fibrillary acidic protein (HR=1.762 (95% CI: 1.367-2.271)) and neurofilament light (HR=1.467 (95% CI: 1.152-1.69)) associated with increased dementia risk. Trajectories following an MCI diagnosis were highly variable with lower dementia conversion rates among Latinx relative to NHW adults, highlighting the need for strong diverse representation in research to capture the range of exposures shaping risk and resilience for cognitive decline. Well-validated blood-based biomarkers are likely to be instrumental for further improving personalized dementia risk predictions.
在不同的队列中轻度认知障碍双向转变的预测因素
轻度认知障碍(MCI)诊断后的轨迹是多种多样的,可能随着时间的推移而波动。在不同的民族和种族群体中,社会因素、医疗合并症和评估程序中的偏见可能导致MCI诊断类别的更大异质性,并影响其对痴呆的预后意义。研究目的是评估非西班牙裔白人(NHW)和拉丁裔老年人中MCI转变的频率和相关变量。多状态马尔可夫模型描述了十年来诊断状态(认知未受损(CU), MCI,痴呆)的转变。使用风险比(HR)和95%置信区间(ci)评估与过渡相关的变量。该研究包括413名参与者(58%为女性,平均年龄72+8岁,52%为拉丁裔)。在MCI诊断后,转化为痴呆和恢复为CU的可能性是一样的。年龄较大,NHW种族,APOE ε4,糖尿病,较低的BMI和较高的神经精神症状与痴呆转化风险增加相关,而年龄较小和较低的神经精神症状与CU逆转相关。在其他因素中,较高的基线血清胶质纤维酸性蛋白(HR=1.762 (95% CI: 1.367-2.271))和神经丝光(HR=1.467 (95% CI: 1.152-1.69))与痴呆风险增加相关。MCI诊断后的轨迹变化很大,与NHW成人相比,拉丁裔的痴呆转换率较低,这突出了在研究中需要强有力的多样化代表,以捕捉形成认知衰退风险和恢复力的暴露范围。经过充分验证的基于血液的生物标志物可能有助于进一步改善个性化的痴呆症风险预测。
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