Amanda I Gonzalez, Lauren C Edwards, Kelsey R Thomas, Alexandra J Weigand, Maria Bordyug, Einat K Brenner, Uriel A Urias, Katherine J Bangen
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Therefore, in the present study, we examined CSF GAP-43 levels among individuals with Obj-SCD cross-sectionally and also examined whether baseline GAP-43 predicts future functional decline.</p><p><strong>Method: </strong>Six hundred forty-four participants from the Alzheimer's Disease Neuroimaging Initiative were divided into six groups based on (a) cognitive status (cognitively unimpaired [CU], Obj-SCD, or MCI) and (b) Aβ status (+ or -).</p><p><strong>Results: </strong>The CU- group had lower baseline GAP-43 than all Aβ+ groups, but not the other Aβ- groups. Higher GAP-43 levels were associated with faster decline across the entire sample. When moderation by group was examined, higher GAP-43 at baseline predicted faster functional decline for the Obj-SCD+ and MCI+ groups, compared to the CU- group.</p><p><strong>Conclusions: </strong>Results extend prior work investigating biomarker associations in Obj-SCD to GAP-43 and show that high baseline CSF GAP-43 is associated with a faster rate of functional decline in Aβ+ individuals who are classified as Obj-SCD or MCI. Importantly, our findings further demonstrate that CSF GAP-43 is associated with early and subtle cognitive changes detectable before the onset of MCI. (PsycInfo Database Record (c) 2025 APA, all rights reserved).</p>","PeriodicalId":19205,"journal":{"name":"Neuropsychology","volume":"39 3","pages":"248-258"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904934/pdf/","citationCount":"0","resultStr":"{\"title\":\"Growth-associated protein 43 is associated with faster functional decline among amyloid-positive individuals with objectively defined subtle cognitive decline and mild cognitive impairment.\",\"authors\":\"Amanda I Gonzalez, Lauren C Edwards, Kelsey R Thomas, Alexandra J Weigand, Maria Bordyug, Einat K Brenner, Uriel A Urias, Katherine J Bangen\",\"doi\":\"10.1037/neu0000981\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Objectively defined subtle cognitive decline (Obj-SCD) is an emerging classification that may identify individuals at risk for future decline and progression to Alzheimer's disease prior to a diagnosis of mild cognitive impairment (MCI). Growth-associated protein 43 (GAP-43), a cerebrospinal fluid (CSF) marker of synaptic dysfunction, has been shown to relate to an increased risk of converting to dementia, although it is unclear whether GAP-43 alterations may be detected in pre-MCI stages. Therefore, in the present study, we examined CSF GAP-43 levels among individuals with Obj-SCD cross-sectionally and also examined whether baseline GAP-43 predicts future functional decline.</p><p><strong>Method: </strong>Six hundred forty-four participants from the Alzheimer's Disease Neuroimaging Initiative were divided into six groups based on (a) cognitive status (cognitively unimpaired [CU], Obj-SCD, or MCI) and (b) Aβ status (+ or -).</p><p><strong>Results: </strong>The CU- group had lower baseline GAP-43 than all Aβ+ groups, but not the other Aβ- groups. Higher GAP-43 levels were associated with faster decline across the entire sample. 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引用次数: 0
摘要
目的:客观定义的细微认知衰退(Obj-SCD)是一种新兴的分类,可以在诊断为轻度认知障碍(MCI)之前识别有未来衰退和进展为阿尔茨海默病风险的个体。生长相关蛋白43 (GAP-43)是一种突触功能障碍的脑脊液(CSF)标志物,已被证明与转化为痴呆的风险增加有关,尽管尚不清楚在mci前期是否可以检测到GAP-43的改变。因此,在本研究中,我们横断面检查了Obj-SCD患者CSF GAP-43水平,并检查了基线GAP-43是否预测未来功能下降。方法:644名来自阿尔茨海默病神经影像学倡议的参与者根据(a)认知状态(认知未受损[CU], Obj-SCD或MCI)和(b) a β状态(+或-)分为六组。结果:CU-组的基线GAP-43低于所有Aβ+组,但低于其他Aβ-组。在整个样本中,GAP-43水平越高,下降速度越快。当检查各组的调节作用时,与CU-组相比,基线时较高的GAP-43预测Obj-SCD+和MCI+组的功能下降更快。结论:研究结果将先前研究Obj-SCD生物标志物相关性的工作扩展到GAP-43,并表明高基线CSF GAP-43与ab β+个体中Obj-SCD或MCI的功能下降速度更快相关。重要的是,我们的研究结果进一步证明CSF GAP-43与MCI发病前可检测到的早期和微妙的认知变化有关。(PsycInfo Database Record (c) 2025 APA,版权所有)。
Growth-associated protein 43 is associated with faster functional decline among amyloid-positive individuals with objectively defined subtle cognitive decline and mild cognitive impairment.
Objective: Objectively defined subtle cognitive decline (Obj-SCD) is an emerging classification that may identify individuals at risk for future decline and progression to Alzheimer's disease prior to a diagnosis of mild cognitive impairment (MCI). Growth-associated protein 43 (GAP-43), a cerebrospinal fluid (CSF) marker of synaptic dysfunction, has been shown to relate to an increased risk of converting to dementia, although it is unclear whether GAP-43 alterations may be detected in pre-MCI stages. Therefore, in the present study, we examined CSF GAP-43 levels among individuals with Obj-SCD cross-sectionally and also examined whether baseline GAP-43 predicts future functional decline.
Method: Six hundred forty-four participants from the Alzheimer's Disease Neuroimaging Initiative were divided into six groups based on (a) cognitive status (cognitively unimpaired [CU], Obj-SCD, or MCI) and (b) Aβ status (+ or -).
Results: The CU- group had lower baseline GAP-43 than all Aβ+ groups, but not the other Aβ- groups. Higher GAP-43 levels were associated with faster decline across the entire sample. When moderation by group was examined, higher GAP-43 at baseline predicted faster functional decline for the Obj-SCD+ and MCI+ groups, compared to the CU- group.
Conclusions: Results extend prior work investigating biomarker associations in Obj-SCD to GAP-43 and show that high baseline CSF GAP-43 is associated with a faster rate of functional decline in Aβ+ individuals who are classified as Obj-SCD or MCI. Importantly, our findings further demonstrate that CSF GAP-43 is associated with early and subtle cognitive changes detectable before the onset of MCI. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
期刊介绍:
Neuropsychology publishes original, empirical research; systematic reviews and meta-analyses; and theoretical articles on the relation between brain and human cognitive, emotional, and behavioral function.