Departments of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Departments of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
J Alzheimers Dis. 2022;90(1):405-417. doi: 10.3233/JAD-220440.
Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes.
Investigate the contributions of vascular factors and cancer to dementia and neuropathology.
Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology.
Participants (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01).
Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.
痴呆症、血管疾病和癌症随着年龄的增长而增加，从而导致复杂的合并症相互作用。了解血管因素和癌症对最高龄人群痴呆风险和神经病理学的影响，可能有助于改善风险修饰和预后。
探究血管因素和癌症对痴呆症和神经病理学的影响。
对前瞻性随访的梅奥诊所参与者进行的纵向临床病理研究，这些参与者在 95 岁以上死亡并接受了尸检。根据痴呆症的情况对参与者进行分层，并根据人口统计学、血管危险因素、癌症和神经病理学进行比较。
参与者（n=161；83%为女性；99%为非西班牙裔白人）≥95 岁（95-106 岁），无论是否患有痴呆症，其人口统计学特征均无差异。无痴呆症（20/72 [28%]）与痴呆症（11/88 [12%]）中 APOE ɛ2 频率较高（p=0.03），但 APOE ɛ4 频率无差异。无痴呆症（31/72 [43%]）与痴呆症（23/89 [26%]）中冠状动脉疾病更为常见（p=0.03），与痴呆症的可能性降低 56%相关（比值比[OR] =0.44 [置信区间（CI）=0.19-0.98]；p=0.04），且神经原纤维缠结/弥漫性斑块较少。糖尿病使痴呆症的可能性增加 8 倍（OR=8.42 [CI=1.39-163]；p=0.02）。糖尿病与更高的脑血管疾病（Dickson 评分；p=0.05）相关。癌症与痴呆症的可能性降低 63%相关（OR=0.37 [CI=0.17-0.78]；p<0.01），且 Braak 分期较低（p=0.01）。
在最高龄人群中，癌症的暴露与痴呆症和缠结病理学的可能性降低相关，而冠状动脉疾病的病史与痴呆症和淀粉样β斑块病理学的可能性降低相关。糖尿病史与痴呆症和脑血管疾病病理学的可能性增加相关。癌症相关机制和血管危险因素降低策略可能会改变最高龄人群的痴呆症风险和神经病理学。
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