Aging related cognitive changes associated with Alzheimer's disease in Down syndrome.
Aging related cognitive changes associated with Alzheimer's disease in Down syndrome.
复制标题
DOI：
10.1002/acn3.571
复制
发表时间：
2018-06
影响因子：
5.3
通讯作者：
Strydom A
中科院分区：
文献类型：
--
作者：
Firth NC;Startin CM;Hithersay R;Hamburg S;Wijeratne PA;Mok KY;Hardy J;Alexander DC;LonDownS Consortium;Strydom A
唐氏综合症（DS）患者患阿尔茨海默病（AD）的遗传风险极高，然而，与痴呆进展相关的认知能力下降过程尚不明确。数据驱动的方法可以从横截面数据中估计长期趋势，同时调整基线能力的变异性，这使DS患者的痴呆评估复杂化。我们将基于事件的模型应用于来自283名DS成人的认知测试数据和知情者评分问卷数据（迄今为止最大的DS认知功能研究），以估计认知下降的顺序和个体的疾病阶段。记忆力、持续注意力/运动协调性和语言流畅性测试的下降发生在早期，表明DS中的AD遵循与其他形式的AD相似的变化模式。后来发现告密者的措施下降。使用由此产生的分期模型，我们发现，临床诊断为痴呆的成年人和APOE 3：4或4：4基因型的成年人更有可能分期较晚，这表明该模型是有效的。我们的研究结果表明，记忆和持续注意力的测试可能是跟踪DS中AD临床前/前驱阶段下降的特别有用的措施，而信息措施可能在后期阶段（即在转化为痴呆或诊断后）有用。这些结果对选择治疗试验的结局指标以延迟或预防DS中AD引起的认知功能下降具有意义。由于临床诊断通常在AD进展后期进行，因此早期评估至关重要。
Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer's disease (AD), however, the course of cognitive decline associated with progression to dementia is ill‐defined. Data‐driven methods can estimate long‐term trends from cross‐sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS. We applied an event‐based model to cognitive test data and informant‐rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals’ disease stage. Decline in tests of memory, sustained attention/motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting that the model is valid. Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant‐measures may be useful in later stages (i.e. during conversion into dementia, or postdiagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.
登录
查看更多内容
DOI：
10.1046/j.1365-2788.2002.00365.x
发表时间：
2002-03-01
影响因子：
3.6
作者：
Krinsky-McHale, SJ;Devenny, DA;Silverman, WP
通讯作者：
Silverman, WP
影响因子：
5.1
作者：
Cosgrave, MP;Tyrrell, J;Lawlor, BA
通讯作者：
Lawlor, BA
DOI：
10.1016/j.jalz.2013.10.003
发表时间：
2014-10
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Donohue MC;Jacqmin-Gadda H;Le Goff M;Thomas RG;Raman R;Gamst AC;Beckett LA;Jack CR Jr;Weiner MW;Dartigues JF;Aisen PS;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
3.1
作者：
Hon, J;Huppert, FA;Watson, P
通讯作者：
Watson, P
DOI：
10.1046/j.1365-2788.2000.00305.x
发表时间：
2000-12-01
影响因子：
3.6
作者：
Devenny, DA;Krinsky-McHale, SJ;Silverman, WP
通讯作者：
Silverman, WP