Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alzheimers Dement. 2020 Jan;16(1):49-59. doi: 10.1016/j.jalz.2019.08.196. Epub 2020 Jan 6.
The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations.
We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.
Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.
Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.
额颞叶变性的研究进展和家族性额颞叶痴呆的纵向评估 这些纵向研究旨在描述常染色体显性突变引起的家族性额颞叶变性的自然史。
我们检查了来自 320 名 MAPT、GRN 和 C9orf72 家族成员的认知表现、行为评分和脑容量，其中包括 102 名非突变携带者、103 名无症状携带者、43 名轻度/可疑症状携带者和 72 名痴呆症携带者。
无症状携带者在所有临床测量中与非携带者的得分相似，但额叶和颞叶体积减少。那些有轻度/可疑损伤的人表现出言语回忆、流畅性和 Trail Making Test 表现下降，情绪和自我监控受损。痴呆症与所有测量的损伤有关。所有携带痴呆症的 MAPT 携带者均出现颞叶萎缩，但除此之外，没有一项单一的认知测试或脑区在所有受试者中均异常。
影像学变化似乎先于家族性额颞叶变性的临床变化，但个体之间的特定早期临床和影像学变化各不相同。
