Hachem Sara, Norton Joanna, Mortamais Marion, Dartigues Jean-François, Helmer Catherine, Tzourio Christophe, Akbaraly Tasnime, Mura Thibault
Institute for Neurosciences of Montpellier INM, INSERM, Univ Montpellier, F-34295 Montpellier, France.
Bordeaux Population Health Center, INSERM U1219, Bordeaux, France.
J Neurol Neurosurg Psychiatry. 2025 May 14;96(6):537-545. doi: 10.1136/jnnp-2025-335928.
Depression has been consistently linked to the onset of dementia, but the temporality and nature of this association-whether causal, prodromal or due to shared pathophysiology-remain unresolved. Longitudinal studies with extended follow-up are necessary to clarify these relationships. This study aimed to characterise the trajectory of depressive symptoms during the 15 years preceding a dementia diagnosis, with particular attention to variations by dementia aetiology.
This nested case-control study was conducted within the Three-City Study cohort, a prospective population-based study initiated in 1999. The cohort included 9294 community-dwelling individuals aged 65 and older, followed for 15 years in three French cities (Bordeaux, Dijon, Montpellier). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale in 1028 dementia cases and 1028 matched controls. Trajectories of depressive symptoms were analysed over the 15 years preceding the index date (dementia diagnosis).
No significant differences in depressive symptomatology (p=0.69) or the frequency of depressive states (OR 1.21, 95% CI 0.51 to 2.87) were observed between cases and controls 12-15 years before the index date. Gradual differences emerged over time, becoming significant 6-8 years prior to dementia onset (p<0.001) and peaking 2 years before the index date (OR 2.93, 95% CI 2.27 to 3.80). These differences were more pronounced in non-Alzheimer's dementia cases.
Depressive symptoms progressively increased in the years leading up to dementia diagnosis, with the most pronounced elevations occurring in non-Alzheimer's dementia.
抑郁症一直与痴呆症的发病有关，但这种关联的时间性和性质——无论是因果关系、前驱症状还是由于共同的病理生理学——仍未得到解决。需要进行长期随访的纵向研究来阐明这些关系。本研究旨在描述痴呆症诊断前15年期间抑郁症状的轨迹，特别关注痴呆症病因导致的差异。
这项巢式病例对照研究在三城市研究队列中进行，该队列是一项于1999年启动的基于人群的前瞻性研究。该队列包括9294名65岁及以上的社区居民，在法国的三个城市（波尔多、第戎、蒙彼利埃）进行了15年的随访。使用流行病学研究中心抑郁量表对1028例痴呆症病例和1028例匹配对照进行抑郁症状评估。分析了索引日期（痴呆症诊断）前15年期间抑郁症状的轨迹。
在索引日期前12 - 15年，病例组和对照组在抑郁症状学方面无显著差异（p = 0.69），抑郁状态的频率也无显著差异（OR 1.21，95%CI 0.51至2.87）。随着时间的推移逐渐出现差异，在痴呆症发病前6 - 8年变得显著（p < 0.001），并在索引日期前2年达到峰值（OR 2.93，95%CI 2.27至3.80）。这些差异在非阿尔茨海默病痴呆症病例中更为明显。
在痴呆症诊断前的几年中，抑郁症状逐渐增加，在非阿尔茨海默病痴呆症中升高最为明显。
