Rennie Anna, Ekman Urban, Shams Sara, Rydén Lina, Samuelsson Jessica, Zettergren Anna, Kern Silke, Oppedal Ketil, Blanc Frédéric, Hort Jakub, Garcia-Ptacek Sara, Antonini Angelo, Lemstra Afina W, Padovani Alessandro, Kramberger Milica Gregoric, Rektorová Irena, Walker Zuzana, Snædal Jón, Pardini Matteo, Taylor John-Paul, Bonanni Laura, Granberg Tobias, Aarsland Dag, Skoog Ingmar, Wahlund Lars-Olof, Kivipelto Miia, Westman Eric, Ferreira Daniel
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77 Stockholm, Sweden.
Medical Unit, Allied Health Professionals Women´s Health, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Brain Commun. 2024 Aug 28;6(5):fcae290. doi: 10.1093/braincomms/fcae290. eCollection 2024.
Co-pathologies are common in dementia with Lewy bodies and other dementia disorders. We investigated cerebrovascular and Alzheimer's disease co-pathologies in patients with dementia with Lewy bodies in comparison with patients with mild cognitive impairment, Alzheimer's disease, mixed dementia, vascular dementia or Parkinson's disease with dementia and cognitively unimpaired participants. We assessed the association of biomarkers of cerebrovascular and Alzheimer's disease co-pathologies with medial temporal atrophy and global cognitive performance. Additionally, we evaluated whether the findings were specific to dementia with Lewy bodies. We gathered a multi-cohort dataset of 4549 participants (dementia with Lewy bodies = 331, cognitively unimpaired = 1505, mild cognitive impairment = 1489, Alzheimer's disease = 708, mixed dementia = 268, vascular dementia = 148, Parkinson's disease with dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of white matter hyperintensities using the Fazekas scale through structural imaging. Alzheimer's disease biomarkers of β-amyloid and phosphorylated tau were assessed in the cerebrospinal fluid for a subsample ( = 2191). Medial temporal atrophy was assessed with visual ratings and global cognition with the mini-mental state examination. Differences and associations were assessed through regression models, including interaction terms. In dementia with Lewy bodies, 43% had a high white matter hyperintensity load, which was significantly higher than that in cognitively unimpaired (14%), mild cognitive impairment (26%) and Alzheimer's disease (27%), but lower than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger than that in cognitively unimpaired and mixed dementia. However, the association between white matter hyperintensities and medial temporal atrophy was non-significant when β-amyloid was included in the model. Instead, β-amyloid predicted medial temporal atrophy in dementia with Lewy bodies, in contrast to the findings in mild cognitive impairment where medial temporal atrophy scores were independent of β-amyloid. Dementia with Lewy bodies had the lowest performance on global cognition, but this was not associated with white matter hyperintensities. In Alzheimer's disease, global cognitive performance was lower in patients with more white matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on β-amyloid-related pathology in our cohort. The associations between biomarkers were overall stronger in dementia with Lewy bodies than in some of the other diagnostic groups.
共病在路易体痴呆和其他痴呆症中很常见。我们研究了路易体痴呆患者的脑血管和阿尔茨海默病共病情况，并与轻度认知障碍患者、阿尔茨海默病患者、混合性痴呆患者、血管性痴呆患者或帕金森病痴呆患者以及认知未受损参与者进行了比较。我们评估了脑血管和阿尔茨海默病共病生物标志物与内侧颞叶萎缩和整体认知表现之间的关联。此外，我们还评估了这些发现是否特定于路易体痴呆。我们从MemClin研究、卡罗林斯卡痴呆影像学研究、哥德堡H70出生队列研究和欧洲路易体痴呆联盟收集了一个包含4549名参与者的多队列数据集（路易体痴呆 = 331例，认知未受损 = 1505例，轻度认知障碍 = 1489例，阿尔茨海默病 = 708例，混合性痴呆 = 268例，血管性痴呆 = 148例，帕金森病痴呆 = 120例）。通过结构成像，使用Fazekas量表对白质高信号进行视觉评分来评估脑血管共病情况。对一个子样本（ = 2191）的脑脊液进行β - 淀粉样蛋白和磷酸化tau蛋白的阿尔茨海默病生物标志物评估。通过视觉评分评估内侧颞叶萎缩，使用简易精神状态检查表评估整体认知。通过回归模型评估差异和关联，包括交互项。在路易体痴呆中，43%的患者白质高信号负荷较高，这显著高于认知未受损者（14%）、轻度认知障碍者（26%）和阿尔茨海默病患者（27%），但低于血管性痴呆患者（62%）。在路易体痴呆中，白质高信号与内侧颞叶萎缩相关，交互项表明这种关联比认知未受损和混合性痴呆更强。然而，当模型中纳入β - 淀粉样蛋白时，白质高信号与内侧颞叶萎缩之间的关联不显著。相反，与轻度认知障碍中内侧颞叶萎缩评分与β - 淀粉样蛋白无关的结果相反，β - 淀粉样蛋白可预测路易体痴呆中的内侧颞叶萎缩。路易体痴呆在整体认知方面表现最差，但这与白质高信号无关。在阿尔茨海默病中，白质高信号较多的患者整体认知表现较低。我们得出结论，白质高信号在路易体痴呆中很常见，并且与内侧颞叶更多萎缩相关，但在我们的队列中这种关联取决于β - 淀粉样蛋白相关病理。路易体痴呆中生物标志物之间的关联总体上比其他一些诊断组更强。
