Wang Sharon, Mimmack Kayden, Cacciamani Federica, Elnemais Fawzy Michael, Munro Catherine, Gatchel Jennifer, Marshall Gad A, Gagliardi Geoffroy, Vannini Patrizia
Department of Neurology, Massachusetts General Hospital, Boston, MA, United States.
Bordeaux Population Health Center, University of Bordeaux, Inserm, Bordeaux, France.
Front Aging Neurosci. 2024 Mar 6;16:1335878. doi: 10.3389/fnagi.2024.1335878. eCollection 2024.
Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross-sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI).
We included 237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with a baseline clinical diagnosis of MCI. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study-partners at baseline and annually over a mean of 4.29 years [standard deviation (SD) = 2.72]. Anosognosia was defined as the study-partner having an ECog score ≥2.5/4 and the participant having an ECog score < 2.5/4 on their baseline measure and their last observation without more than two consecutive deviating observations during the follow-up period. The 12-item study-partner-rated Neuropsychiatric Inventory determined the presence or absence of specific NPS. Survival analyses were performed to analyze the frequency and temporal onset of NPS over time in individuals with and without anosognosia.
Thirty-eight out of 237 participants displayed anosognosia. Groups had similar lengths of follow-up at baseline ( > 0.9), though participants with anosognosia had lower MMSE scores ( = 0.049) and a higher proportion of amyloid-positivity using PET ( < 0.001. At baseline, the frequencies of agitation ( = 0.029 and disinhibition ( < 0.001 were higher in the anosognosia group compared to the non-anosognosia group. Survival analyses showed earlier onset of seven of the 12 NPS in the anosognosia group < 0.001).
Loss of awareness for cognitive decline is associated with greater frequency and earlier onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process for anosognosia and NPS, a finding that needs to be addressed in future studies.
认知衰退失认症（又称疾病感缺失）和神经精神症状（NPS）在阿尔茨海默病（AD）痴呆患者中都很常见，即使在前驱期也是如此，并且可能会加重功能障碍并对照料者负担产生负面影响。尽管这些症状对患者及其照料者有很大影响，但我们对它们在整个AD谱系中的发展情况了解有限。在此，我们探讨了轻度认知障碍（MCI）患者中疾病感缺失与NPS之间的横断面和纵向关联。
我们纳入了来自阿尔茨海默病神经影像倡议（ADNI）的237名参与者，他们的基线临床诊断为MCI。使用日常认知（ECog）问卷分数来衡量参与者及其研究伙伴在基线时以及平均4.29年[标准差（SD）=2.72]的年度随访中的主诉。疾病感缺失被定义为研究伙伴在基线测量时的ECog分数≥2.5/4，而参与者在基线测量时以及随访期间最后一次观察时的ECog分数<2.5/4，且在随访期间没有超过两次连续的偏差观察。由研究伙伴评定的12项神经精神症状问卷确定了特定NPS的存在与否。进行生存分析以分析有和没有疾病感缺失的个体中NPS随时间的发生频率和时间发病情况。
237名参与者中有38名表现出疾病感缺失。两组在基线时的随访时间相似（>0.9），尽管有疾病感缺失的参与者的简易精神状态检查表（MMSE）分数较低（=0.049），并且使用正电子发射断层扫描（PET）检测到的淀粉样蛋白阳性比例较高（<0.001）。在基线时，与无疾病感缺失组相比，疾病感缺失组中激越（=0.029）和去抑制（<0.001）的频率更高。生存分析显示，疾病感缺失组中12种NPS中的7种发病更早（<0.001）。
在MCI参与者中，认知衰退失认症与随着时间推移NPS的更高频率和更早发病相关。这些结果支持了疾病感缺失和NPS可能存在潜在共同神经生理过程的假设，这一发现需要在未来的研究中加以探讨。
