From the Normandie Univ (E.K., A.P., E.T., S.D., M.V., D.V., G.C.), UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders," Institut Blood and Brain @ Caen-Normandie, Cyceron, France; Memory and Aging Center (R.L.J.), Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco; Département de Recherche Clinique (D.V.), CHU Caen-Normandie; and Service de Neurologie (V.d.L.S.), CHU de Caen, France.
Neurology. 2023 Jun 13;100(24):e2454-e2465. doi: 10.1212/WNL.0000000000207338. Epub 2023 Apr 21.
Studies are sparse regarding the association between the informant-reported subjective memory decline (informant report) and Alzheimer disease (AD) biomarkers. This study thus aimed at determining the clinical relevance of the informant report throughout the AD clinical continuum, by assessing its specific relationships with amyloid deposition, cognition, and neurodegeneration.
Participants from the Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce (IMAP+) primary cohort and the Alzheimer Disease Neuroimaging Initiative (ADNI) replication cohort were included; all underwent multimodal neuroimaging and neuropsychological assessments. Follow-up data of IMAP+ participants over up to 36 months were also used for longitudinal analyses. The informant report was measured with the Cognitive Difficulties Scale (IMAP+) and Everyday Cognition (ADNI). General linear models were used to assess the cross-sectional associations between the informant report and amyloid-PET, cognitive performances, and neurodegeneration (atrophy and hypometabolism) in Alzheimer signature areas; while longitudinal links were assessed in IMAP+ with linear mixed-effects models.
A total of 110 IMAP+ participants were included, including 32 cognitively unimpaired older individuals (controls, age: 70.91 ± 6.57 years, female: 50%), 25 patients with subjective cognitive decline (SCD, 65.88 ± 6.64, 40%), 35 with mild cognitive impairment (MCI, 72.49 ± 7.5, 34%), and 18 with Alzheimer-type dementia (AD dementia, 68.17 ± 8.59, 28%). Seven hundred thirty-one ADNI participants were included, including 157 controls (74.21 ± 5.95, 55%), 84 with SCD (72.00 ± 5.41, 63%), 369 with MCI (71.84 ± 7.4, 44%), and 121 with AD dementia (74.29 ± 7.75, 40%). In IMAP+, a higher informant report strongly correlated to greater amyloid-PET, specifically in patients with MCI (β = 0.48, = 0.003), and to lower cognitive performance in patients with SCD (global cognition, β = -0.41, = 0.04) and MCI (memory, β = -0.37, = 0.03). Findings in patients with MCI were replicated in the ADNI (amyloid-PET, β = 0.25, < 0.001; memory, β = -0.22, < 0.001) and extended to neurodegeneration in AD signature areas (β = -0.2, < 0.001). Longitudinal analyses in IMAP+ showed links with global cognitive decline over time in patients with MCI (estimate -0.74, SE 0.26, = 0.005) and SCD (estimate -0.36, SE 0.26, = 0.02) where a higher baseline informant report also predicted an increased amyloid-PET over time (estimate 0.008, SE 0.003, = 0.02).
Altogether, our findings suggest that the informant report is particularly relevant in patients with MCI where it strongly relates to higher amyloid-PET, indicative of impairment due to AD.
ClinicalTrials.gov Identifier: NCT01638949.
有关信息提供者报告的主观记忆减退（信息提供者报告）与阿尔茨海默病（AD）生物标志物之间关联的研究很少。因此，本研究旨在通过评估信息提供者报告与淀粉样蛋白沉积、认知和神经退行性变的具体关系，确定其在 AD 临床连续体中的临床相关性。
纳入了来自早期阿尔茨海默病的多模态成像研究（IMAP+）的主要队列和阿尔茨海默病神经影像学倡议（ADNI）的复制队列的参与者；所有参与者均接受了多模态神经影像学和神经心理学评估。还使用了 IMAP+参与者长达 36 个月的随访数据进行纵向分析。信息提供者报告使用认知困难量表（IMAP+）和日常认知（ADNI）进行测量。使用一般线性模型评估信息提供者报告与淀粉样蛋白-PET、认知表现和阿尔茨海默病特征区域的神经退行性变（萎缩和低代谢）之间的横断面关联；而在 IMAP+中，使用线性混合效应模型评估纵向关联。
共纳入 110 名 IMAP+参与者，包括 32 名认知正常的老年人（对照组，年龄：70.91±6.57 岁，女性：50%）、25 名有主观认知减退的患者（SCD，65.88±6.64，40%）、35 名轻度认知障碍患者（MCI，72.49±7.5，34%）和 18 名阿尔茨海默病型痴呆患者（AD 痴呆，68.17±8.59，28%）。纳入了 731 名 ADNI 参与者，包括 157 名对照组（74.21±5.95，55%）、84 名 SCD 患者（72.00±5.41，63%）、369 名 MCI 患者（71.84±7.4，44%）和 121 名 AD 痴呆患者（74.29±7.75，40%）。在 IMAP+中，较高的信息提供者报告与更大的淀粉样蛋白-PET 强烈相关，特别是在 MCI 患者中（β=0.48， =0.003），并且与 SCD 患者的认知表现较低相关（整体认知，β=-0.41， =0.04）和 MCI 患者（记忆，β=-0.37， =0.03）。ADNI 中的发现（淀粉样蛋白-PET，β=0.25， ＜0.001；记忆，β=-0.22， ＜0.001））和在 AD 特征区域的神经退行性变中得到扩展（β=-0.2， ＜0.001）。IMAP+中的纵向分析显示，在 MCI 患者中（估计值-0.74，SE 0.26， =0.005）和 SCD 患者中（估计值-0.36，SE 0.26， =0.02），与全球认知能力随时间下降有关，其中较高的基线信息提供者报告也预测了随时间推移淀粉样蛋白-PET 的增加（估计值 0.008，SE 0.003， =0.02）。
总之，我们的研究结果表明，信息提供者报告在 MCI 患者中特别相关，因为它与更高的淀粉样蛋白-PET 强烈相关，这表明 AD 导致的损害。
临床试验.gov 标识符：NCT01638949。
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