From the Department of Neurobiology (R.W., E.J.L., G.K., L.B., L.F., C.Q.), Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm University; Division of Radiology (A.L.), Department of Clinical Science, Intervention and Technology, Karolinska University Hospital at Huddinge; Department of Neuroradiology (A.L.), Karolinska University Hospital, Stockholm; and Stockholm Gerontology Research Center (L.F.), Stockholm, Sweden.
Neurology. 2018 Oct 16;91(16):e1487-e1497. doi: 10.1212/WNL.0000000000006355. Epub 2018 Sep 19.
To explore the differential associations of neurodegeneration and microvascular lesion load with cognitive decline and dementia in older people and the modifying effect of the genotype on these associations.
A sample of 436 participants (age ≥ 60 years) was derived from the population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, and clinically examined at baseline (2001-2003) and 3 occasions during the 9-year follow-up. At baseline, we assessed microvascular lesion load using a summary score for MRI markers of lacunes, white matter hyperintensities (WMHs), and perivascular spaces and neurodegeneration load for markers of enlarged ventricles, smaller hippocampus, and smaller gray matter. We assessed cognitive function using the Mini-Mental State Examination (MMSE) test and diagnosed dementia following the , 4th edition criteria. We analyzed data using linear mixed-effects, mediation, and random-effects Cox models.
During the follow-up, 46 participants were diagnosed with dementia. Per 1-point increase in microvascular lesion and neurodegeneration score (range 0-3) was associated with multiple adjusted β-coefficients of -0.35 (95% confidence interval, -0.51 to -0.20) and -0.44 (-0.56 to -0.32), respectively, for the MMSE score and multiple adjusted hazard ratios of 1.68 (1.12-2.51) and 2.35 (1.58-3.52), respectively, for dementia; carrying ε4 reinforced the associations with MMSE decline. WMH volume changes during the follow-up mediated 66.9% and 12.7% of the total association of MMSE decline with the baseline microvascular score and neurodegeneration score, respectively.
Both cerebral microvascular lesion and neurodegeneration loads are strongly associated with cognitive decline and dementia. The cognitive decline due to microvascular lesions is exacerbated by ε4 and is largely attributed to progression and development of microvascular lesions.
探讨老年人认知衰退和痴呆与神经退行性变和微血管病变负荷的差异关联，以及基因型对这些关联的修饰作用。
从斯德哥尔摩 Kungsholmen 的基于人群的瑞典国家老龄化和护理研究中抽取了 436 名参与者（年龄≥60 岁）作为样本，并在基线（2001-2003 年）和 9 年随访期间的 3 次临床检查中进行了检查。在基线时，我们使用 MRI 标记物腔隙、白质高信号（WMH）和血管周围空间以及扩大脑室、较小海马体和较小灰质的标记物的综合评分来评估微血管病变负荷。我们使用 Mini-Mental State Examination（MMSE）测试评估认知功能，并根据 ，第 4 版标准诊断痴呆症。我们使用线性混合效应、中介和随机效应 Cox 模型分析数据。
在随访期间，有 46 名参与者被诊断为痴呆症。微血管病变和神经退行性病变评分每增加 1 分（范围 0-3），与 MMSE 评分的多变量调整后 β 系数分别为 -0.35（95%置信区间，-0.51 至 -0.20）和 -0.44（-0.56 至 -0.32），与痴呆症的多变量调整后危险比分别为 1.68（1.12-2.51）和 2.35（1.58-3.52）；携带 ε4 增强了与 MMSE 下降的关联。在随访期间，WMH 体积变化介导了 MMSE 下降与基线微血管评分和神经退行性病变评分总关联的 66.9%和 12.7%。
脑微血管病变和神经退行性病变负荷均与认知衰退和痴呆密切相关。ε4 加重了微血管病变引起的认知衰退，且主要归因于微血管病变的进展和发展。
