Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco.
Department of Biostatistics, University of California, San Francisco.
JAMA Neurol. 2018 Jun 1;75(6):728-737. doi: 10.1001/jamaneurol.2018.0395.
Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation.
To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD).
DESIGN, SETTING, AND PARTICIPANTS: This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017.
Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts.
A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD) were included in the study. The groups were not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3% female; lvPPA, 56.0% female; amnestic AD, 57.0% female; P = .30) but differed on non-right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3% white; lvPPA, 99.0% white; amnestic AD, 80.0% white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0% expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this rate was greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of global cognition and a more right-lateralized pattern of atrophy.
Nonlanguage mathematical and visuospatial LDs were associated with focal, visuospatial predominant neurodegenerative clinical syndromes. This finding supports the hypothesis that neurodevelopmental differences in specific brain networks are associated with phenotypic manifestation of later-life neurodegenerative disease.
先前有研究报道原发性进行性失语症（PPA）患者的语言学习障碍（LD）患病率增加。本研究假设，除语言网络外，局灶性神经退行性综合征患者（如后部皮质萎缩症 [PCA]），由于其主要的视觉空间表现，非语言性 LD 的发生率会更高。
与 logopenic 变异型 PPA（lvPPA）和遗忘型阿尔茨海默病（AD）相比，在 PCA 患者的大样本队列中调查 LD（语言和/或数学和视觉空间）的患病率和类型。
设计、设置和参与者：本病例对照研究回顾了来自一个以大学为基础的神经退行性疾病诊所和研究中心的 279 份医疗记录，以了解 LD 病史，包括 PCA 患者（n=95）、lvPPA 患者（n=84）和匹配的遗忘型 AD 患者（n=100）。未排除任何记录。比较了有和无 LD 的 PCA 患者的认知和神经影像学特征。对 1999 年 3 月 1 日至 2014 年 8 月 31 日就诊的患者的记录进行了回顾，发现 95 例 PCA 病例和 84 例 lvPPA 病例。然后从同一时期选择了 100 例遗忘型 AD 患者作为比较，按年龄、性别和疾病严重程度与各组进行匹配。数据分析于 2013 年 9 月 8 日至 2017 年 11 月 6 日进行。
所有队列中总 LD 病史的患病率和语言、数学或视觉空间 LD 病史的患病率。
共有 179 例非典型 AD 病例（95 例 PCA 和 84 例 lvPPA）和 100 例疾病对照组病例（遗忘型 AD）纳入研究。各组在首次就诊时的平均（SD）年龄（PCA，61.9[7.0]岁；lvPPA，65.1[8.7]岁；遗忘型 AD，64.0[12.6]岁；P=0.08）、首次出现症状时的平均（SD）年龄（PCA，57.5[7.0]岁；lvPPA，61.1[9.0]岁；遗忘型 AD，59.6[13.7]岁；P=0.06）或性别（PCA，66.3%女性；lvPPA，56.0%女性；遗忘型 AD，57.0%女性；P=0.30）无统计学差异，但非右利手（PCA，18.3%；lvPPA，20.2%；遗忘型 AD，7.7%；P=0.04）、种族/民族（PCA，88.3%白人；lvPPA，99.0%白人；遗忘型 AD，80.0%白人；P<0.001）和平均（SD）受教育程度（PCA，15.7[3.2]年；lvPPA，16.2[3.3]年；遗忘型 AD，14.8[3.5]年；P=0.02）存在差异。95 例 PCA 患者中有 18 例（18.9%）报告有 LD 病史，高于遗忘型 AD 患者（3/100[3.0%]）（P<0.001）和一般人群（10.0%）（P=0.007）预期发病率。在 PCA 组中，13 例（13.7%）患者存在非语言性数学和/或视觉空间 LD，这一比例高于遗忘型 AD 患者（1/100[1.0%]；P<0.001）和 lvPPA 患者（2/84[2.4%]；P=0.006），且高于一般人群（6.0%）的数学 LD 预期发病率（P=0.003）。与无 LD 的 PCA 患者相比，有 LD 的患者整体认知功能保存更好，且萎缩模式更偏向右侧。
非语言性数学和视觉空间 LD 与局灶性、以视觉空间为主的神经退行性临床综合征有关。这一发现支持了这样一种假设，即特定脑网络的神经发育差异与晚年神经退行性疾病的表型表现有关。
