Dementia Research Group, Faculty of Health Sciences, University of Bristol, Southmead Hospital, Level 1 Learning & Research Building, Bristol, BS10 5NB, UK.
Douglas Institute, Department of Psychiatry, McGill University, Montreal, Canada.
Alzheimers Res Ther. 2023 Sep 12;15(1):153. doi: 10.1186/s13195-023-01299-2.
Depression and dementia are both common diseases. Although new cases of depression are more common in younger adults, there is a second peak at the age of 50 years suggesting a different pathological process. Late-life depression (LLD) is associated with dementia. However, it remains unclear whether depression represents a dementia prodrome or is a true risk factor for its development. LLD is thought to have a vascular component and this may be a possible link between depression and dementia. We hypothesised that later-life depression is a prodromal manifestation of dementia and would therefore be associated with more AD, and/or ischaemic brain abnormalities that are present in earlier-life depression or in age- and sex-matched controls.
We assessed post-mortem orbitofrontal cortex and dorsolateral pre-frontal cortex from 145 individuals in 4 groups: 28 18-50-year-olds with depression, 30 older individuals (ages 51-90) with depression, 28 with early AD (Braak tangle stages III-IV) and 57 matched controls (17 early-life, 42 later-life). Levels of Aβ, phospho-tau and α-synuclein were assessed by immunohistochemistry and ELISA. To quantify chronic ischaemia, VEGF, MAG and PLP1 were measured by ELISA. To assess pericyte damage, PDGFRB was measured by ELISA. For blood-brain barrier leakiness, JAM-A, claudin 5 and fibrinogen were measured by ELISA. To quantity endothelial activation, the ratio of ICAM1:collagen IV was assessed by immunohistochemistry.
There was no evidence of chronic cerebral hypoperfusion or increased Aβ/tau in either depression group. There was also no indication of pericyte damage, increased blood-brain barrier leakiness or endothelial activation in the OFC or DLPFC in the depression groups.
Contrary to some previous findings, we have not found evidence of impaired vascular function or increased Aβ in LLD. Our study had a relatively small sample size and limitations in the availability of clinical data. These results suggest that depression is a risk factor for dementia rather than an early manifestation of AD or a consequence of cerebral vascular insufficiency.
抑郁症和痴呆症都是常见疾病。虽然新病例的抑郁症在年轻人中更为常见，但在 50 岁时会出现第二个高峰，这表明存在不同的病理过程。老年期抑郁症（LLD）与痴呆症有关。然而，目前尚不清楚抑郁症是否代表痴呆症的前驱期，或者是否是其发展的真正危险因素。LLD 被认为具有血管成分，这可能是抑郁症和痴呆症之间的一个可能联系。我们假设，老年期抑郁症是痴呆症的前驱期表现，因此与更多的 AD 以及/或存在于早发性抑郁症或年龄和性别匹配的对照组中的缺血性脑异常相关。
我们评估了来自 4 个组的 145 个人的眶额皮层和背外侧前额叶皮层：28 名 18-50 岁的抑郁症患者、30 名 51-90 岁的抑郁症患者、28 名早期 AD（Braak 缠结阶段 III-IV）患者和 57 名匹配的对照者（17 名早发性，42 名晚发性）。通过免疫组织化学和 ELISA 评估 Aβ、磷酸化 tau 和 α-突触核蛋白的水平。为了量化慢性缺血，通过 ELISA 测量 VEGF、MAG 和 PLP1。为了评估周细胞损伤，通过 ELISA 测量 PDGFRB。为了评估血脑屏障通透性，通过 ELISA 测量 JAM-A、claudin 5 和纤维蛋白原。为了量化内皮细胞激活，通过免疫组织化学评估 ICAM1：胶原 IV 的比值。
在任何抑郁症组中，都没有发现慢性脑灌注不足或 Aβ/tau 增加的证据。在抑郁症组的眶额皮层或背外侧前额叶皮层中，也没有发现周细胞损伤、血脑屏障通透性增加或内皮细胞激活的迹象。
与一些先前的发现相反，我们没有发现 LLD 中血管功能受损或 Aβ 增加的证据。我们的研究样本量相对较小，并且临床数据的可用性有限。这些结果表明，抑郁症是痴呆症的危险因素，而不是 AD 的早期表现或脑血管不足的后果。
