Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Division of Clinical Sciences Helsingborg, Department of Clinical Sciences Lund, Lund University, Helsingborg, Sweden; Clinical Department of Psychiatry, Helsingborg Hospital, Helsingborg, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
Biol Psychiatry. 2022 Jul 1;92(1):34-43. doi: 10.1016/j.biopsych.2022.01.012. Epub 2022 Jan 31.
The impact of Alzheimer's disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages.
Cognitively unimpaired older adults (N = 356) enrolled in the prospective Swedish BioFINDER study were examined. Neuropsychiatric assessments encompassed the Apathy Evaluation Scale and the Hospital Anxiety and Depression Scale, performed biennially (together with tests of global cognition) for up to 8 years. Biomarkers were measured in cerebrospinal fluid or plasma at baseline. Magnetic resonance imaging quantified white matter lesions. We used linear mixed-effect models to test associations between baseline AD biomarkers (for amyloid-β [Aβ], tau, and neurodegeneration) and white matter lesions with longitudinal neuropsychiatric symptoms (apathy, anxiety, and depressive symptoms). We also tested associations between changes in cognition and changes in neuropsychiatric symptoms. Finally, we tested if change in cognition mediated the effects of different brain pathologies on neuropsychiatric symptoms.
Aβ pathology at baseline was associated with increasing levels of apathy (β = -0.284, p = .005) and anxiety (β = -0.060, p = .011) longitudinally. More rapid decline of cognition over time was related to increasing levels of apathy. The effects of baseline Aβ pathology on longitudinal apathy were partly mediated by changes in cognitive performance (proportion mediated 23%).
Aβ pathology may drive the development of both apathy and anxiety in very early stages of AD, largely independent of cognitive change. The effect of Aβ on apathy is only partially conveyed by worse cognition. Together, these findings highlight certain neuropsychiatric symptoms as early manifestations of AD.
阿尔茨海默病（AD）病理学和认知缺陷对纵向神经精神症状的影响尚不清楚，尤其是在疾病早期阶段。
本研究纳入了前瞻性瑞典生物发现者研究中的认知未受损的老年受试者（N=356）。神经精神评估包括淡漠评估量表和医院焦虑抑郁量表，每两年评估一次（同时评估整体认知），最长持续 8 年。基线时测量了脑脊液或血浆中的生物标志物。磁共振成像定量了白质病变。我们使用线性混合效应模型来检验基线 AD 生物标志物（用于检测淀粉样蛋白-β[Aβ]、tau 和神经退行性变）和白质病变与纵向神经精神症状（淡漠、焦虑和抑郁症状）之间的相关性。我们还检验了认知变化与神经精神症状变化之间的相关性。最后，我们检验了认知变化是否在不同脑病理学对神经精神症状的影响中起中介作用。
基线时的 Aβ 病理学与纵向淡漠（β=-0.284，p=0.005）和焦虑（β=-0.060，p=0.011）水平的升高有关。随着时间的推移，认知能力下降得更快与淡漠水平升高有关。基线 Aβ 病理学对纵向淡漠的影响部分通过认知表现的变化来介导（介导比例为 23%）。
Aβ 病理学可能在 AD 的极早期阶段导致淡漠和焦虑的发展，且与认知变化基本独立。Aβ 对淡漠的影响仅部分通过认知能力下降来传递。这些发现共同强调了某些神经精神症状是 AD 的早期表现。
