时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
The strength of evidence nonetheless differs across these connections: the inverse associations rest primarily on human epidemiological and neuropathological evidence, whereas most molecular links derive from experimental models, and whether any materially contributes to population-level inverse comorbidity remains unproven.；Thus, the key question is not whether one mechanism explains the cancer–AD paradox, but which mechanisms operate in particular cancer, treatment, tissue, and disease contexts.；In the aging brain, by contrast, the stress-inducible HSF1–HSP response becomes attenuated, reducing chaperone reserve and increasing vulnerability to Aβ, tau, and other aggregation-prone proteins (51–53).Autophagy–lysosome function determines whether proteotoxic stress is successfully buffered or progresses toward aggregate accumulation.
方法
Here, we instead propose a treatment-aware, multilevel framework that separates three distinct questions: the population-level inverse association, the systemic consequences of cancer and its treatment, and the molecular mechanisms that may connect cancer and AD.；In a cohort of 3,021,508 adults aged ≥60 years, a previous cancer diagnosis was associated with a 25% lower subsequent dementia risk (HR 0.75, 95% CI 0.74–0.76) after adjustment for demographic, lifestyle, and cardiometabolic factors.；In a community-based autopsy cohort, a history of cancer was associated with lower odds of advanced Braak neurofibrillary tangle stages, neuritic and diffuse plaques, and cerebral amyloid angiopathy, but not with TDP-43, α-synuclein, or cerebrovascular pathology (8).
核心结论
The heterogeneous associations reported for breast cancer hormone-modulating therapy and prostate cancer androgen-deprivation therapy therefore demonstrate why cancer diagnosis, disease severity, and treatment exposure must be evaluated separately (3, 4).Recent reviews have primarily synthesized epidemiological and Mendelian-randomization evidence or quantified associations between cancer treatments and dementia risk (2, 5).；The latter currently provides the most direct experimentally demonstrated tumor-to-brain mechanism linking cancer with AD pathology.；Overall, the inverse pattern is modest, cancer-specific, and sensitive to survival, ascertainment, treatment exposure, and the definition of AD outcomes.
局限
This pattern is neither universal nor necessarily causal, however, because its magnitude varies across cancer types, dementia subtypes, populations, and analytical designs and is influenced by competing mortality, diagnostic surveillance, survivor selection, and the long preclinical phases of both diseases.；However, the association disappeared in landmark analyses restricted to women surviving more than five years, arguing against a durable inverse association.；However, reduced prostate-specific antigen screening and diagnostic investigation after dementia may partly explain this apparent inverse association (18).Several large observational studies associate ADT with increased dementia risk.
对本项目的价值
中高价值：属「衰老细胞清除 / SASP 轴」方向；细胞衰老 / senolytics / SASP栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.1/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 50,742 字符，题名指纹 0.89，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：癌症-阿尔茨海默逆共病：从流行病学到蛋白自组装
- 英文标题：Cancer-Alzheimer inverse comorbidity from epidemiology to protein self-assembly.
- 期刊与标识：Frontiers in endocrinology · PMID 42974248 · DOI 10.3389/fendo.2026.1992522 · PMC PMC13725551