METHODS: We selected 214 patients with AD neuropathological change (ADNC) with no LB (n = 102), ADNC with LB (ADNC+LB) (n = 77), PART with no LB (n = 22) and PART with LB (PART+LB) (n = 13) with ante-mortem volumetric MRI from the National Alzheimer\'s Coordinating Center, after exclusion of other neurodegenerative pathologies. Dementia severity was compared using Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). Cortical and subcortical MRI volume residuals were compared between groups after correction for age. Statistical significance was considered at p-value < 0.05 after false discovery rate correction for multiple comparisons.
RESULTS: We found that ADNC, ADNC+LB and PART+LB presented similar levels of dementia severity, whereas PART with no LB was the least affected group. MRI revealed higher atrophy of the right frontal operculum and amygdala in ADNC+LB compared to ADNC. ADNC and ADNC+LB showed increased atrophy in regions across all cortical lobes, hippocampus, amygdala and putamen compared to PART, but did not reveal significant differences compared to PART+LB. Interestingly, PART+LB showed higher atrophy of the frontal poles bilaterally, right superior frontal gyrus, left frontal operculum and right putamen compared to PART.
CONCLUSIONS: Altogether, these results suggest that LB co-pathology contributes to frontal lobe regional atrophy in ADNC and likely drives it in PART. Particularly in PART+LB, it suggests that cognitive impairment might derive from alpha-synuclein pathology rather than tauopathy. These findings indicate that LB pathology determines disease severity within the PART- and AD-continuums.
方法:我们选择了214例无LB的AD神经病理变化(ADNC)患者(n=102),ADNC与LB(ADNC+LB)(n=77),没有LB的部分(n=22)和LB部分(PART+LB)(n=13)与来自国家阿尔茨海默氏症协调中心的死前体积MRI,排除其他神经退行性病变后。使用临床痴呆评定量表框总和(CDR-SB)比较痴呆严重程度。校正年龄后,比较各组之间的皮质和皮质下MRI体积残留。在多个比较的错误发现率校正后,在p值<0.05时考虑统计学显著性。
结果:我们发现ADNC,ADNC+LB和PART+LB表现出相似的痴呆严重程度,而没有LB的PART是受影响最小的组。MRI显示,与ADNC相比,ADNCLB中右额叶和杏仁核的萎缩程度更高。ADNC和ADNC+LB显示所有皮质叶区域的萎缩增加,海马体,杏仁核和壳核与部分相比,但与PART+LB相比没有显着差异。有趣的是,PART+LB显示双侧额叶高度萎缩,右额上回,与PART相比,左额脑膜和右壳核。
结论:总而言之,这些结果表明,LB共同病理有助于ADNC的额叶区域萎缩,并可能在PART引起。特别是在Part+LB中,这提示认知障碍可能源自α-突触核蛋白病理而非tau蛋白病.这些发现表明LB病理学决定了PART-和AD-连续体中的疾病严重程度。