Kang Matthew J Y, Eratne Dhamidhu, Loi Samantha M, Dang Christa, Santillo Alexander F, Zetterberg Henrik, Blennow Kaj, Mitchell Philip B, Hopwood Malcolm, Malpas Charles B, Velakoulis Dennis
Neuropsychiatry Centre The Royal Melbourne Hospital Melbourne Victoria Australia.
Department of Psychiatry The University of Melbourne Melbourne Victoria Australia.
Alzheimers Dement (Amst). 2025 Jul 29;17(3):e70151. doi: 10.1002/dad2.70151. eCollection 2025 Jul-Sep.
Apathy and affective neuropsychiatric symptoms (NPS) are prevalent in Alzheimer's disease (AD), yet their neurobiological cause is still unclear. We examined associations between plasma neurofilament light chain (NfL) and tau pathology (p-tau181) with apathy and affective symptoms in mild cognitive impairment (MCI) and AD dementia.
This longitudinal study analyzed data from 781 participants with MCI and AD dementia enrolled in ADNI, with annual blood samples collected over 4 years. NPS were assessed via the Neuropsychiatric Interview (NPI), and biomarker trajectories were analyzed using mixed-effects models.
Elevated plasma NfL levels were associated with apathy, anxiety and depression in MCI and AD dementia, with apathy linked to a significantly higher rate of NfL increase, indicating accelerated neurodegeneration.
Apathy and affective symptoms may indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression.
Apathy and affective neuropsychiatric symptoms (NPS) are highly prevalent in clinical Alzheimer's disease (AD).The presence of apathy, depression or anxiety was associated with higher plasma levels of neurofilament light chain (NfL).Apathy was associated with an accelerated increase in plasma NfL levels over time.Apathy and affective NPS were not associated with p-tau181 levels in plasma.
冷漠和情感性神经精神症状（NPS）在阿尔茨海默病（AD）中很常见，但其神经生物学原因仍不清楚。我们研究了血浆神经丝轻链（NfL）和tau病理（p-tau181）与轻度认知障碍（MCI）和AD痴呆中的冷漠及情感症状之间的关联。
这项纵向研究分析了参与阿尔茨海默病神经成像计划（ADNI）的781名MCI和AD痴呆患者的数据，在4年中每年采集血样。通过神经精神访谈（NPI）评估NPS，并使用混合效应模型分析生物标志物轨迹。
血浆NfL水平升高与MCI和AD痴呆中的冷漠、焦虑和抑郁相关，冷漠与NfL升高的显著更高比率相关，表明神经退行性变加速。
冷漠和情感症状可能表明AD中更大的神经退行性负担，独立于tau相关病理。冷漠与血浆NfL的更陡峭上升相关，表明疾病进展更具侵袭性。
冷漠和情感性神经精神症状（NPS）在临床阿尔茨海默病（AD）中高度普遍。冷漠、抑郁或焦虑的存在与血浆神经丝轻链（NfL）水平升高相关。随着时间推移冷漠与血浆NfL水平加速升高相关。冷漠和情感性NPS与血浆p-tau181水平无关。
