Spanish National Center for Cardiovascular Research, Madrid, Spain.
Spanish National Center for Cardiovascular Research, Madrid, Spain; Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Lancet Healthy Longev. 2023 Sep;4(9):e487-e498. doi: 10.1016/S2666-7568(23)00134-4.
Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals.
The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [F]fluorodeoxyglucose ([F]FDG)-PET, and annual percentage change in [F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood-based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach.
This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49·8 years [IQR 46·1-52·2]; 309 [84%] men, 61 [16%] women; median follow-up 4·7 years [IQR 4·2-5·2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [F]FDG uptake compared with low risk (β=-0·008 [95% CI -0·013 to -0·002]; p=0·040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (β=0·198 [0·008 to 0·740]; p=0·050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (β=-0·269 [95% CI -0·509 to -0·027]; p=0·029).
Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life.
Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Santander Bank, Pro-CNIC Foundation, BrightFocus Foundation, BBVA Foundation, "la Caixa" Foundation.
心血管疾病和痴呆症通常在晚期同时存在。然而，研究中年期动脉粥样硬化及其危险因素与大脑健康之间相互作用的纵向研究却很少。我们旨在描述中年无症状个体中脑葡萄糖代谢、亚临床动脉粥样硬化和心血管危险因素之间的纵向关联。
早期亚临床动脉粥样硬化进展（PESA）研究是一项西班牙纵向观察性队列研究，纳入了 4184 名年龄在 40-54 岁的无症状个体（NCT01410318）。有亚临床动脉粥样硬化的参与者接受了纵向脑[F]氟脱氧葡萄糖([F]FDG)-PET，评估[F]FDG 摄取的年度百分比变化（主要结局）。心血管风险用 SCORE2 量化，亚临床动脉粥样硬化用三维血管超声（暴露因素）量化。采用多变量回归和线性混合效应模型评估结局与暴露因素之间的关联。此外，还定量了血液神经病理学生物标志物，并进行了中介分析。二级分析采用错误发现率（FDR）方法进行了多次比较校正。
这项纵向研究纳入了 PESA 亚队列的 370 名参与者（基线时的中位年龄为 49.8 岁[四分位距 46.1-52.2]；309[84%]名男性，61[16%]名女性；中位随访时间为 4.7 年[四分位距 4.2-5.2]）。基线扫描于 2013 年 3 月 6 日至 2015 年 1 月 21 日进行，随访扫描于 2017 年 11 月 24 日至 2019 年 8 月 7 日进行。持续的高心血管疾病风险与皮质[F]FDG 摄取的加速下降相关，而低风险则无此关联（β=-0.008[95%CI -0.013 至 -0.002]；p=0.040），血浆神经丝轻链作为神经退行性变的标志物，通过 20%的中介作用解释了这种关联（β=0.198[0.008 至 0.740]；p=0.050）。此外，亚临床颈动脉粥样硬化的进展与阿尔茨海默病大脑区域的[F]FDG 摄取进一步下降相关，而这与心血管风险无关（β=-0.269[95%CI -0.509 至 -0.027]；p=0.029）。
中年无症状个体中持续存在的高心血管疾病风险和亚临床颈动脉粥样硬化已经出现了脑代谢下降，这表明中年期保持心血管健康可能有助于降低晚年神经退行性疾病的负担。
西班牙科学与创新部、西班牙卡洛斯三世健康研究所、桑坦德银行、Pro-CNIC 基金会、美国光明基金会、西班牙毕尔巴鄂比斯开银行基金会、“la Caixa”基金会。
