From the Departments of Psychiatry and Psychology (T.J.F., O.P.), Neurology (J.A.V.G., N.R.G.-R., R.J.U., Z.K.W.), and Neuroscience (M.E.M., O.A.R., D.W.D.) Mayo Clinic, Jacksonville, FL; Department of Psychiatry (N.A.), Yokohama University Medical Center, Japan; and Departments of Neurology (B.F.B., J.G.-R., D.S.K., R.C.P.), Health Sciences Research (J.A.A.), Radiology (K.K.), Laboratory Medicine and Pathology (J.E.P., R.R.R.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN.
Neurology. 2020 Jul 14;95(2):e155-e165. doi: 10.1212/WNL.0000000000009763. Epub 2020 Jun 19.
To determine whether Lewy body disease subgroups have different clinical profiles.
Participants had dementia, autopsy-confirmed transitional or diffuse Lewy body disease (TLBD or DLBD) (n = 244), or Alzheimer disease (AD) (n = 210), and were seen at least twice (mean follow-up 6.2 ± 3.8 years). TLBD and DLBD groups were partitioned based on the presence or absence of neocortical neurofibrillary tangles using Braak staging. Four Lewy body disease subgroups and AD were compared on clinical features, dementia trajectory, and onset latency of probable dementia with Lewy bodies (DLB) or a DLB syndrome defined as probable DLB or dementia with one core feature of parkinsonism or probable REM sleep behavior disorder.
In TLBD and DLBD without neocortical tangles, diagnostic sensitivity was strong for probable DLB (87% TLBD, 96% DLBD) and the DLB syndrome (97% TLBD, 98% DLBD) with median latencies <1 year from cognitive onset, and worse baseline attention-visual processing but better memory-naming scores than AD. In DLBD with neocortical tangles, diagnostic sensitivity was 70% for probable DLB and 77% for the DLB syndrome with respective median latencies of 3.7 years and 2.7 years from cognitive onset, each associated with tangle distribution. This group had worse baseline attention-visual processing than AD, but comparable memory-naming impairment. TLBD with neocortical tangles had 48% diagnostic sensitivity for probable DLB and 52% for the DLB syndrome, with median latencies >6 years from cognitive onset, and were cognitively similar to AD. Dementia trajectory was slowest for TLBD without neocortical tangles, and fastest for DLBD with neocortical tangles.
The phenotypic expression of DLB was associated with the distribution of α-synuclein and tau pathology.
确定路易体病亚组是否具有不同的临床特征。
参与者患有痴呆症，经尸检证实为过渡性或弥漫性路易体病（TLBD 或 DLBD）（n = 244）或阿尔茨海默病（AD）（n = 210），并至少接受了两次随访（平均随访 6.2 ± 3.8 年）。TLBD 和 DLBD 组根据是否存在新皮质神经纤维缠结，使用 Braak 分期进行分组。将四个路易体病亚组和 AD 进行比较，比较内容包括临床特征、痴呆轨迹以及可能的路易体痴呆（DLB）或定义为可能的 DLB 或具有帕金森病一个核心特征或可能 REM 睡眠行为障碍之一的 DLB 综合征的发病潜伏期。
在无新皮质缠结的 TLBD 和 DLBD 中，对于可能的 DLB（TLBD 为 87%，DLBD 为 96%）和 DLB 综合征（TLBD 为 97%，DLBD 为 98%），诊断敏感性较强，从认知发作开始的中位潜伏期<1 年，且基线注意力-视觉处理能力较差，但记忆-命名评分优于 AD。在具有新皮质缠结的 DLBD 中，可能的 DLB 的诊断敏感性为 70%，DLB 综合征的诊断敏感性为 77%，从认知发作开始的中位潜伏期分别为 3.7 年和 2.7 年，每个亚组均与缠结分布相关。该组的基线注意力-视觉处理能力比 AD 差，但记忆-命名损伤相当。具有新皮质缠结的 TLBD 对于可能的 DLB 的诊断敏感性为 48%，对于 DLB 综合征的诊断敏感性为 52%，从认知发作开始的中位潜伏期>6 年，认知表现与 AD 相似。无新皮质缠结的 TLBD 的痴呆轨迹最慢，而具有新皮质缠结的 DLBD 的痴呆轨迹最快。
DLB 的表型表达与α-突触核蛋白和 tau 病理学的分布有关。
