Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
J Alzheimers Dis. 2020;76(3):1017-1027. doi: 10.3233/JAD-200011.
Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown to associate with hallmarks of neurodegeneration.
The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology.
We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBI- n = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming Neuropsychiatric Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years.
Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016).
These findings suggest MBI is a clinical proxy of early phase neurodegeneration with putative utility in identifying those at dementia risk. MBI can be used as a case ascertainment approach to capture those at high risk for cognitive decline and dementia, and is an important construct for clinicians dealing with cognitive and neuropsychiatric symptomatology in older adults.
评估老年人的神经精神症状（NPS）对于确定痴呆风险很重要。轻度行为障碍（MBI）是认知能力下降和痴呆的高危状态，其特征是晚年出现新的 NPS。MBI 的痴呆发病率明显高于晚年精神疾病。然而，其作为神经退行性变的替代指标的效用尚未得到证实。血浆神经丝轻链（NfL）是轴突损伤的验证生物标志物，并且已经显示与神经退行性变的特征相关联。
本研究旨在确定 NfL 变化率与 MBI 症状存在之间的关联。
我们评估了 MBI 与阿尔茨海默病神经影像学倡议（Alzheimer's Disease Neuroimaging Initiative）中无痴呆参与者队列（n = 584；MBI + n = 190，MBI- n = 394）中 NfL 变化的关联。MBI 是通过使用已发表的算法对神经精神病学问卷项目进行转换来确定的。在 2 年内计算 NfL 的变化。
时间*MBI 状态是唯一显著的交互作用，可以预测 NfL 浓度的变化（F（1,574） = 4.59，p = 0.032），即使在控制了年龄、轻度认知障碍和人口统计学因素之后也是如此。对 2 年内新出现 MBI 的 64 名参与者进行重新分类的分析同样表明，NfL 的增加更大（F（1,574） = 5.82，p = 0.016）。
这些发现表明 MBI 是早期神经退行性变的临床替代指标，具有识别痴呆风险的潜在效用。MBI 可用于作为病例确定方法来捕获那些认知能力下降和痴呆风险较高的人群，并且对于处理老年人认知和神经精神症状的临床医生来说是一个重要的概念。
