Pink Anna, Stokin Gorazd B, Bartley Mairead M, Roberts Rosebud O, Sochor Ondrej, Machulda Mary M, Krell-Roesch Janina, Knopman David S, Acosta Jazmin I, Christianson Teresa J, Pankratz V Shane, Mielke Michelle M, Petersen Ronald C, Geda Yonas E
From Mayo Clinic Translational Neuroscience and Aging Program (A.P., J.K.-R., J.I.A., Y.E.G.), and Departments of Psychiatry & Psychology (Y.E.G.) and Neurology (Y.E.G.), Mayo Clinic, Scottsdale, AZ; Departments of Neurology (M.M.B., D.S.K., R.C.P.) and Psychiatry & Psychology (M.M. Machulda), Divisions of Epidemiology (R.O.R., M.M. Mielke, R.C.P., Y.E.G.) and Biomedical Statistics and Informatics (T.J.C., V.S.P.), Department of Health Sciences Research, Mayo Clinic, Rochester, MN; International Clinical Research Center (A.P., G.B.S., O.S., J.K.-R., Y.E.G.), Brno, Czech Republic; and Paracelsus Medical University (A.P.), Salzburg, Austria.
Neurology. 2015 Mar 3;84(9):935-43. doi: 10.1212/WNL.0000000000001307. Epub 2015 Feb 4.
To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI).
We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity.
Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95% CI = 1.24-3.91; test for additive interaction, p < 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95% CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia.
Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia.
研究在患有轻度认知障碍（MCI）的人群中，生物变量（APOEε4）、神经精神症状与新发痴呆风险之间基于人群的相互作用。
我们对梅奥诊所衰老研究中纳入的332例患有MCI（年龄70岁及以上）的参与者进行了前瞻性随访，中位随访时间为3年。MCI和痴呆的诊断由专家共识小组根据已发表的标准，在审查神经、认知和其他相关数据后做出。使用神经精神科问卷在基线时确定神经精神症状。我们使用以年龄为时间尺度的Cox比例风险模型来计算风险比（HR）和95%置信区间（CI）。模型对性别、教育程度和合并症进行了校正。
基线时的激越、夜间行为、抑郁和淡漠显著增加了新发痴呆的风险。我们观察到APOEε4与抑郁之间存在相加相互作用（联合效应HR = 2.21；95%CI = 1.24 - 3.91；相加相互作用检验，p < 0.001）；以及APOEε4与淡漠之间存在相加相互作用（联合效应HR = 1.93；95%CI = 0.93 - 3.98；相加相互作用检验，p = 0.031）。焦虑、易怒和食欲/进食与新发痴呆风险增加无关。
在患有MCI的病例中，基线时的激越、夜间行为、抑郁和淡漠增加了新发痴呆的风险。抑郁或淡漠与APOEε4之间存在协同相互作用，进一步增加了新发痴呆的风险。
